{"id":2011,"date":"2018-06-20T19:11:22","date_gmt":"2018-06-20T19:11:22","guid":{"rendered":"http:\/\/www.drshevchuk.com.ua\/?p=2011"},"modified":"2018-06-20T19:16:09","modified_gmt":"2018-06-20T19:16:09","slug":"proximal-hypospadias-and-a-novel-wt1-variant-when-should-genetic-testing-be-considered-%d0%b3%d0%b5%d0%bd%d0%b5%d1%82%d0%b8%d1%87%d0%bd%d0%b5-%d1%82%d0%b5%d1%81%d1%82%d1%83%d0%b2%d0%b0","status":"publish","type":"post","link":"http:\/\/www.drshevchuk.com.ua\/?p=2011","title":{"rendered":"Proximal Hypospadias and a Novel\u00a0WT1\u00a0Variant: When Should Genetic Testing Be Considered?\/ \u0413\u0435\u043d\u0435\u0442\u0438\u0447\u043d\u0435 \u0442\u0435\u0441\u0442\u0443\u0432\u0430\u043d\u043d\u044f \u043f\u0440\u0438 \u043f\u0440\u043e\u043a\u0441\u0438\u043c\u0430\u043b\u044c\u043d\u0456\u0439 \u0433\u0456\u043f\u043e\u0441\u043f\u0430\u0434\u0456\u0457"},"content":{"rendered":"<div class=\"panel-row-wrapper panel-row-first row\">\n<div class=\"top-wrapper\">\n<div class=\"panel-panel panel-region-top\">\n<div class=\"inside\">\n<div class=\"panel-pane pane-highwire-article-citation ped-toc-section\">\n<div class=\"pane-content\">\n<div id=\"node137729\" class=\"highwire-article-citation highwire-citation-type-highwire-article\" data-node-nid=\"137729\" data-pisa=\"pediatrics;141\/Supplement_5\/S491\" data-pisa-master=\"pediatrics;peds.2017-0230\" data-apath=\"\/pediatrics\/141\/Supplement_5\/S491.atom\">\n<div class=\"highwire-cite highwire-cite-highwire-article highwire-citation-aap-jcore-citation clearfix\">\n<div class=\"highwire-cite-overline\">\n<div class=\"toc-section\"><a class=\"pediatrics-toc-section\" href=\"http:\/\/pediatrics.aappublications.org\/\">Pediatrics<\/a><\/div>\n<div class=\"pub-date\"><a class=\"article-issue-link\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\">April 2018, VOLUME 141 \/ ISSUE Supplement 5<\/a><\/div>\n<div class=\"series-title-content\">\n<div class=\"series-title-prefix\">From the American Academy of Pediatrics<\/div>\n<div class=\"series-title\">Case Report<\/div>\n<\/div>\n<\/div>\n<h1 class=\"highwire-cite-title page-title\">Proximal Hypospadias and a Novel\u00a0<em>WT1<\/em>\u00a0Variant: When Should Genetic Testing Be Considered?<\/h1>\n<div class=\"highwire-cite-authors\"><span class=\"highwire-citation-authors\"><span class=\"highwire-citation-author first\" data-delta=\"0\">Elizabeth Dabrowski<\/span>,\u00a0<span class=\"highwire-citation-author\" data-delta=\"1\">Amy E. Armstrong<\/span>,\u00a0<span class=\"highwire-citation-author\" data-delta=\"2\">Elizabeth Leeth<\/span>,\u00a0<span class=\"highwire-citation-author\" data-delta=\"3\">Emilie Johnson<\/span>,\u00a0<span class=\"highwire-citation-author\" data-delta=\"4\">Earl Cheng<\/span>,\u00a0<span class=\"highwire-citation-author\" data-delta=\"5\">Yasmin Gosiengfiao<\/span>,\u00a0<span class=\"highwire-citation-author\" data-delta=\"6\">Courtney Finlayson<\/span><\/span><\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"panel-separator\"><\/div>\n<div class=\"panel-pane pane-highwire-panel-tabs pane-panels-ajax-tab-tabs panels-ajax-tabs-once-processed\">\n<div class=\"pane-content\">\n<div class=\"item-list\">\n<ul class=\"tabs inline panels-ajax-tab\">\n<li class=\"first active\"><a class=\"panels-ajax-tab-tab panels-ajax-tabs-once-processed panels-ajax-tabs-first-loaded hw-panels-ajax-tabs-once-processed\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491\" data-panel-name=\"jnl_aap_tab_art\" data-target-id=\"highwire_article_tabs\" data-entity-context=\"node:137729\" data-trigger=\"\" data-url-enabled=\"1\">Article<\/a><\/li>\n<li><a class=\"panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.figures-only\" data-panel-name=\"jnl_aap_tab_data\" data-target-id=\"highwire_article_tabs\" data-entity-context=\"node:137729\" data-trigger=\"figures-only\" data-url-enabled=\"1\">Figures &amp; Data<\/a><\/li>\n<li><a class=\"panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491..info\" data-panel-name=\"jnl_aap_tab_info\" data-target-id=\"highwire_article_tabs\" data-entity-context=\"node:137729\" data-trigger=\".info\" data-url-enabled=\"1\">Info &amp; Metrics<\/a><\/li>\n<li class=\"last\"><a class=\"panels-ajax-tab-tab panels-ajax-tabs-once-processed hw-panels-ajax-tabs-once-processed\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.comments\" data-panel-name=\"jnl_aap_tab_elets\" data-target-id=\"highwire_article_tabs\" data-entity-context=\"node:137729\" data-trigger=\"comments\" data-url-enabled=\"1\">Comments<\/a><\/li>\n<\/ul>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<div class=\"panel-row-wrapper row\">\n<div class=\"main-content-wrapper col-narrow-18\">\n<div class=\"panel-panel panel-region-content\">\n<div class=\"inside\">\n<div class=\"panel-pane pane-highwire-panel-tabs-container\">\n<div class=\"pane-content\">\n<div id=\"panels-ajax-tab-container-highwire_article_tabs\" class=\"panels-ajax-tab-container\" data-panels-ajax-tab-preloaded=\"jnl_aap_tab_art\">\n<div class=\"panels-ajax-tab-wrap-jnl_aap_tab_art\">\n<div class=\"panel-display panel-1col clearfix\">\n<div class=\"panel-panel panel-col\">\n<div>\n<div class=\"panel-pane pane-highwire-variant-link\">\n<div class=\"pane-content\"><a class=\"aap-download-pdf link-icon\" title=\"Download PDF\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.full-text.pdf\" target=\"_blank\" rel=\"noopener\"><i class=\"aap-icon-page-pdf\"><\/i>Download PDF<\/a><\/div>\n<\/div>\n<div class=\"panel-separator\"><\/div>\n<div class=\"panel-pane pane-highwire-markup\">\n<div class=\"pane-content\">\n<div class=\"highwire-markup\">\n<div id=\"content-block-markup\" data-highwire-cite-ref-tooltip-instance=\"highwire_reflinks_tooltip\">\n<div class=\"article fulltext-view \">\n<div id=\"abstract-2\" class=\"section abstract\">\n<h2>Abstract<\/h2>\n<p id=\"p-2\">We present a case of an infant with proximal hypospadias, penoscrotal transposition, and bilaterally descended testes found to have a clinically significant\u00a0<em>WT1<\/em>\u00a0gene alteration on a customized disorder of sex development genetic panel in which 62 genes associated with 46, XY disorders of sex development were evaluated. This diagnosis led to early screening for and diagnosis and treatment of Wilms tumor. Patients with proximal hypospadias are not routinely evaluated by genetic testing, and when initial hormonal analyses are within normal ranges for a typical male patient, the genital atypia is usually attributed to an isolated anatomic abnormality. There is no consensus among urologists, endocrinologists, or geneticists regarding when genetic testing is warranted in these patients or the extent of genetic testing that should be pursued. However, given advances in genetic testing and the discovery of more genetic variants, the genetic evaluation of infants with proximal hypospadias should be considered on an individual patient basis. Only with continued evaluation and the identification of further genetic variants can we establish future parameters for genetic evaluation in patients with proximal hypospadias and more appropriately counsel patients and their families regarding the implications of these variants.<\/p>\n<\/div>\n<ul>\n<li id=\"glossary-1\" class=\"fn\">Abbreviations:\n<dl id=\"def-list-1\">\n<dt id=\"def-item-1\">DDS<span class=\"def-item-dt-sep\">\u00a0\u2014<\/span><\/dt>\n<dd>Denys-Drash syndrome<\/dd>\n<dt id=\"def-item-2\">DSD<span class=\"def-item-dt-sep\">\u00a0\u2014<\/span><\/dt>\n<dd>disorder of sex development<\/dd>\n<dt id=\"def-item-3\">FS<span class=\"def-item-dt-sep\">\u00a0\u2014<\/span><\/dt>\n<dd>Frasier syndrome<\/dd>\n<dt id=\"def-item-4\">WT<span class=\"def-item-dt-sep\">\u00a0\u2014<\/span><\/dt>\n<dd>Wilms tumor<\/dd>\n<\/dl>\n<\/li>\n<\/ul>\n<p id=\"p-3\">Disorders of sex development (DSDs) are congenital conditions caused by atypical sexual ontogenesis secondary to chromosomal, gonadal, or anatomic abnormalities.<a id=\"xref-ref-1-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-1\"><sup>1<\/sup><\/a>\u00a0DSDs affect \u223c1 in 2000 to 5000 individuals and encompass an array of phenotypes and genotypes, from atypical genitalia in infancy to primary amenorrhea in adolescence to infertility in adulthood.<a id=\"xref-ref-2-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-2\"><sup>2<\/sup><\/a>\u00a0Determining an etiology in infants with atypical genitalia is challenging. Historically, \u223c10% to 15% of patients with a 46, XY DSD received a genetic diagnosis via testing of\u00a0<em>SRY<\/em>\u00a0and\u00a0<em>NR5A1<\/em>; however, through exome sequencing panels, diagnostic yield increases up to 35%.<a id=\"xref-ref-3-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-3\"><sup>3<\/sup><\/a>\u00a0In the past, genetic testing had been reserved for the most severe cases. As genetic technology advances, testing becomes more affordable and new pathogenic mutations are discovered; there is now increasing consideration of genetic evaluation in less severe forms of genital anomalies. Disorders once considered purely anatomic abnormalities, such as isolated hypospadias or isolated cryptorchidism, have not been routinely evaluated with genetic testing. Among patients with hypospadias, there are no clear guidelines regarding when genetic laboratory evaluation is indicated or the extent of evaluation.<a id=\"xref-ref-1-2\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-1\"><sup>1<\/sup><\/a><\/p>\n<p id=\"p-4\">We present a patient with hypospadias, penoscrotal transposition, and bilaterally descended testes diagnosed with a novel\u00a0<em>WT1<\/em>\u00a0variant identified through a customized, multigene panel (XomeDxSlice; GeneDx, Gaithersburg, MD). The\u00a0<em>WT1<\/em>\u00a0gene, on chromosome 11p13, plays an important role in early embryonic development of the renal and urogenital systems. Clinical presentations of\u00a0<em>WT1<\/em>\u00a0pathogenic variants encompass a spectrum of features, including genital anomalies, renal failure, Wilms tumor (WT), gonadoblastoma, and syndromes such as Denys-Drash syndrome (DDS), Frasier syndrome (FS), and isolated nephrotic syndrome. Full deletions of the\u00a0<em>WT1<\/em>\u00a0gene result in WAGR syndrome (Wilms tumor, aniridia, genital anomalies, and intellectual disability). We demonstrate how identification of a novel, likely pathogenic\u00a0<em>WT1<\/em>\u00a0variant led to early screening, detection, and treatment of WT.<\/p>\n<div id=\"sec-1\" class=\"section cases\">\n<h2 class=\"\">Case Presentation<\/h2>\n<p id=\"p-5\">A 7-day-old infant was referred to our multidisciplinary DSD clinic. At the 20-week fetal ultrasound, sex was indeterminate; the pregnancy was otherwise uneventful. The infant was delivered without incident via induced vaginal delivery. A detailed family history was noncontributory, albeit maternal history was limited by adoption. An initial examination revealed a healthy appearing infant who was appropriate for gestational age in weight, length, and head circumference with no apparent anomalies other than on the genitourinary examination, which revealed penoscrotal transposition with a well-formed phallic structure and perineal hypospadias. The labioscrotal folds were rugated and fused posteriorly; testes were palpable in the scrotum bilaterally. The karyotype was 46, XY, and an ultrasound revealed bilaterally descended testes and no Mullerian structures.<\/p>\n<p id=\"p-6\">Multiple laboratory evaluations were performed within the first month of life (see\u00a0<a id=\"xref-table-wrap-1-1\" class=\"xref-table\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#T1\">Table 1<\/a>). Testosterone levels were typical of a male infant. Evaluation of the adrenal axis revealed no abnormalities consistent with congenital adrenal hyperplasia. The testosterone-to-dihydrotestosterone ratio was not consistent with a diagnosis of 5-\u03b1 reductase deficiency. Thus, more common causes of 46, XY DSDs were excluded. This, in conjunction with normal hormone levels for a male patient and the presence of bilaterally descended testes, led clinicians to believe the abnormal genitourinary findings were most likely due to an isolated anatomic abnormality. However, a genetic anomaly remained possible, and the family was counseled regarding testing options. They decided to proceed with a customized XomeDxSlice that evaluates 62 genes known to be associated with DSDs.<\/p>\n<div id=\"T1\" class=\"table pos-float\">\n<div class=\"table-inline table-callout-links\">\n<div class=\"callout\">\n<p>View this table:<\/p>\n<ul class=\"callout-links\">\n<li class=\"view-inline first\"><a class=\"table-expand-inline highwireTablesMarkupProcessor-processed\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long##\" data-table-url=\"\/highwire\/markup\/137769\/expansion?postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed&amp;table-expand-inline=1\">View inline<\/a><\/li>\n<li class=\"view-popup last\"><a class=\"colorbox colorbox-load table-expand-popup init-colorbox-processed cboxElement\" href=\"http:\/\/pediatrics.aappublications.org\/highwire\/markup\/137769\/expansion?width=1000&amp;height=500&amp;iframe=true&amp;postprocessors=highwire_tables%2Chighwire_reclass%2Chighwire_figures%2Chighwire_math%2Chighwire_inline_linked_media%2Chighwire_embed\" rel=\"gallery-fragment-tables\">View popup<\/a><\/li>\n<\/ul>\n<\/div>\n<\/div>\n<div class=\"table-caption\">\n<p><span class=\"table-label\">TABLE 1<\/span><\/p>\n<p id=\"p-24\" class=\"first-child\">Laboratory Results<\/p>\n<div class=\"sb-div caption-clear\"><\/div>\n<\/div>\n<\/div>\n<p id=\"p-7\">Testing identified a novel, heterozygous\u00a0<em>WT1<\/em>\u00a0variant in exon 1 of the\u00a0<em>WT1<\/em>\u00a0gene (NM_024426.4, GRCh37\/UCSChg19), p.Glu153Ter (E153X): c.457G&gt;T. This previously unreported\u00a0<em>WT1<\/em>\u00a0variant resulting in a premature stop codon was predicted to cause loss of normal protein function via protein truncation or nonsense-mediated messenger RNA decay.<a id=\"xref-ref-4-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-4\"><sup>4<\/sup><\/a><sup>\u2013<\/sup><a id=\"xref-ref-6-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-6\"><sup>6<\/sup><\/a>\u00a0Although our patient\u2019s mutation was not previously described and therefore of unclear clinical significance, similar variants in the same region were reported as pathogenic with variable phenotypes.<a id=\"xref-ref-7-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-7\"><sup>7<\/sup><\/a>\u00a0The clinical phenotype and likely pathogenic variant in our patient prompted further evaluation of known\u00a0<em>WT1<\/em>\u00a0variant anomalies, including WT screening.<\/p>\n<p id=\"p-8\">Initial ultrasound at 5 months of life revealed mild enlargement of the left kidney with nonspecific areas of increased echogenicity; a repeat ultrasound, 3 weeks later, revealed 2 focal areas of abnormal parenchyma in the left kidney and a new cluster of small cortical cysts in the right kidney. Through MRI, multifocal, bilateral renal lesions consistent with nephroblastomatosis as well as a dominant, spherical lesion in the upper-right kidney measuring 2.8 \u00d7 1.9 \u00d7 2.5 cm were shown, which were concerning for WT (<a id=\"xref-fig-1-1\" class=\"xref-fig\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#F1\">Fig 1A<\/a>). Repeat imaging before initiation of therapy revealed significant interval enlargement of multiple bilateral renal masses, the largest measuring 4.3 \u00d7 4.3 \u00d7 4.1 cm, suggestive of bilateral WT (<a id=\"xref-fig-1-2\" class=\"xref-fig\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#F1\">Fig 1B<\/a>); however, MRI cannot always differentiate between WT and nephroblastomatosis.<a id=\"xref-ref-8-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-8\"><sup>8<\/sup><\/a>\u00a0Biopsy specimens from the dominant right renal lesion obtained after 6 weeks of chemotherapy revealed intralobar nephrogenic rests and favorable histology for WT (<a id=\"xref-fig-2-1\" class=\"xref-fig\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#F2\">Fig 2<\/a>). After another 6 weeks of chemotherapy, the patient underwent right radical nephrectomy, and biopsy specimens from the left renal lesions revealed nephrogenic rests. The patient continues on chemotherapy and is currently in complete remission.<\/p>\n<div id=\"F1\" class=\"fig pos-float type-figure odd\">\n<div class=\"highwire-figure\">\n<div class=\"fig-inline-img-wrapper\">\n<div class=\"fig-inline-img\"><a class=\"highwire-fragment fragment-images colorbox-load highwireFiguresMarkupProcessor-processed cboxElement\" title=\"A, MRI (abdomen) revealing multiple bilateral renal lesions compatible with nephroblastomatosis and a lesion (arrow) in the upper-right kidney concerning for neoplastic rest or WT because of the dominant size and spherical shape. B, Repeat MRI before treatment (5.5 weeks later) revealing significant enlargement of multiple bilateral renal masses suggestive of bilateral WT.\" href=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F1.large.jpg?width=800&amp;height=600&amp;carousel=1\" rel=\"gallery-fragment-images-1303102369\" data-figure-caption=\"&lt;div class=&quot;highwire-markup&quot;&gt;A, MRI (abdomen) revealing multiple bilateral renal lesions compatible with nephroblastomatosis and a lesion (arrow) in the upper-right kidney concerning for neoplastic rest or WT because of the dominant size and spherical shape. B, Repeat MRI before treatment (5.5 weeks later) revealing significant enlargement of multiple bilateral renal masses suggestive of bilateral WT.&lt;\/div&gt;\"><span class=\"hw-responsive-img\"><img decoding=\"async\" loading=\"lazy\" class=\"highwire-fragment fragment-image lazyloaded colorbox-2011\" src=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F1.medium.gif\" alt=\"FIGURE 1\" width=\"440\" height=\"208\" data-src=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F1.medium.gif\" \/><\/span><\/a><\/div>\n<\/div>\n<ul class=\"highwire-figure-links inline\">\n<li class=\"download-fig first\"><a class=\"highwire-figure-link highwire-figure-link-download\" title=\"Download FIGURE 1\" href=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F1.large.jpg?download=true\">Download figure<\/a><\/li>\n<li class=\"new-tab\"><a class=\"highwire-figure-link highwire-figure-link-newtab\" href=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F1.large.jpg\" target=\"_blank\" rel=\"noopener\">Open in new tab<\/a><\/li>\n<li class=\"download-ppt last\"><a class=\"highwire-figure-link highwire-figure-link-ppt\" href=\"http:\/\/pediatrics.aappublications.org\/highwire\/powerpoint\/137747\">Download powerpoint<\/a><\/li>\n<\/ul>\n<\/div>\n<div class=\"fig-caption\">\n<p><span class=\"fig-label\">FIGURE 1<\/span><\/p>\n<p id=\"p-26\" class=\"first-child\">A, MRI (abdomen) revealing multiple bilateral renal lesions compatible with nephroblastomatosis and a lesion (arrow) in the upper-right kidney concerning for neoplastic rest or WT because of the dominant size and spherical shape. B, Repeat MRI before treatment (5.5 weeks later) revealing significant enlargement of multiple bilateral renal masses suggestive of bilateral WT.<\/p>\n<div class=\"sb-div caption-clear\"><\/div>\n<\/div>\n<\/div>\n<div id=\"F2\" class=\"fig pos-float type-figure odd\">\n<div class=\"highwire-figure\">\n<div class=\"fig-inline-img-wrapper\">\n<div class=\"fig-inline-img\"><a class=\"highwire-fragment fragment-images colorbox-load highwireFiguresMarkupProcessor-processed cboxElement\" title=\"A, Intralobar nephrogenic rest, characterized by the presence of immature nephrogenic elements admixed with native renal tubules (H&amp;E, magnification \u00d7100). B, A WT with predominant stromal morphology is shown, consisting of spindle cells with skeletal muscle differentiation admixed with a few isolated epithelial structures (H&amp;E, magnification \u00d740). H&amp;E, haemotoxylin and eosin.\" href=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F2.large.jpg?width=800&amp;height=600&amp;carousel=1\" rel=\"gallery-fragment-images-1303102369\" data-figure-caption=\"&lt;div class=&quot;highwire-markup&quot;&gt;A, Intralobar nephrogenic rest, characterized by the presence of immature nephrogenic elements admixed with native renal tubules (H&amp;E, magnification \u00d7100). B, A WT with predominant stromal morphology is shown, consisting of spindle cells with skeletal muscle differentiation admixed with a few isolated epithelial structures (H&amp;E, magnification \u00d740). H&amp;E, haemotoxylin and eosin.&lt;\/div&gt;\"><span class=\"hw-responsive-img\"><img decoding=\"async\" loading=\"lazy\" class=\"highwire-fragment fragment-image lazyloaded colorbox-2011\" src=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F2.medium.gif\" alt=\"FIGURE 2\" width=\"292\" height=\"440\" data-src=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F2.medium.gif\" \/><\/span><\/a><\/div>\n<\/div>\n<ul class=\"highwire-figure-links inline\">\n<li class=\"download-fig first\"><a class=\"highwire-figure-link highwire-figure-link-download\" title=\"Download FIGURE 2\" href=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F2.large.jpg?download=true\">Download figure<\/a><\/li>\n<li class=\"new-tab\"><a class=\"highwire-figure-link highwire-figure-link-newtab\" href=\"http:\/\/pediatrics.aappublications.org\/content\/pediatrics\/141\/Supplement_5\/S491\/F2.large.jpg\" target=\"_blank\" rel=\"noopener\">Open in new tab<\/a><\/li>\n<li class=\"download-ppt last\"><a class=\"highwire-figure-link highwire-figure-link-ppt\" href=\"http:\/\/pediatrics.aappublications.org\/highwire\/powerpoint\/137815\">Download powerpoint<\/a><\/li>\n<\/ul>\n<\/div>\n<div class=\"fig-caption\">\n<p><span class=\"fig-label\">FIGURE 2<\/span><\/p>\n<p id=\"p-27\" class=\"first-child\">A, Intralobar nephrogenic rest, characterized by the presence of immature nephrogenic elements admixed with native renal tubules (H&amp;E, magnification \u00d7100). B, A WT with predominant stromal morphology is shown, consisting of spindle cells with skeletal muscle differentiation admixed with a few isolated epithelial structures (H&amp;E, magnification \u00d740). H&amp;E, haemotoxylin and eosin.<\/p>\n<div class=\"sb-div caption-clear\"><\/div>\n<\/div>\n<\/div>\n<\/div>\n<div id=\"sec-2\" class=\"section discussion\">\n<h2 class=\"\">Discussion<\/h2>\n<p id=\"p-9\">Our patient\u2019s novel\u00a0<em>WT1<\/em>\u00a0variant, p.E153X, initially interpreted as likely pathogenic, was reclassified as pathogenic after parental test results were negative and genitourinary anomalies in association with WT development in our patient were identified. As discussed, there is a wide array of phenotypic variability associated with\u00a0<em>WT1<\/em>\u00a0alterations, including isolated WT and syndromic and nonsyndromic disorders involving various degrees of genitourinary abnormalities, ocular abnormalities, intellectual disabilities, and nephrotic syndrome.<a id=\"xref-ref-9-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-9\"><sup>9<\/sup><\/a><\/p>\n<p id=\"p-10\"><em>WT1<\/em>\u00a0mutations, once thought to cause distinct syndromes such as DDS or FS, are now considered to encompass a phenotypic spectrum that may correlate with the location and type of alteration.<a id=\"xref-ref-7-2\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-7\"><sup>7<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-10-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-10\"><sup>10<\/sup><\/a>\u00a0Historically, both DDS and FS present with ambiguous genitalia or complete sex reversal in XY individuals secondary to complete or partial gonadal dysgenesis. DDS has been reported in association with heterozygous germline missense variants in\u00a0<em>WT1<\/em>\u00a0exons 8 or 9, which also have high rates of nephropathy.<a id=\"xref-ref-10-2\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-10\"><sup>10<\/sup><\/a>\u00a0However, mutations of all types and in all exons have been reported in patients diagnosed with DDS or partial DDS.<a id=\"xref-ref-10-3\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-10\"><sup>10<\/sup><\/a><sup>\u2013<\/sup><a id=\"xref-ref-14-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-14\"><sup>14<\/sup><\/a>\u00a0<em>WT1<\/em>\u00a0exon mutations are associated with WT in 36% to 88% of patients with bilateral WT, and these mutations are highest in truncating variants.<a id=\"xref-ref-13-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-13\"><sup>13<\/sup><\/a>\u00a0Progressive renal failure occurs in 74% of those with WT, with milder phenotypes associated with mutations outside exons 8 and 9.<a id=\"xref-ref-7-3\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-7\"><sup>7<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-10-4\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-10\"><sup>10<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-15-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-15\"><sup>15<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-16-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-16\"><sup>16<\/sup><\/a>\u00a0FS is classically associated with intron 9 splice-site variants, resulting in gonadoblastoma and nephropathy without WT. However, both gonadoblastoma and WT have been reported in a single patient, indicating that DDS and FS are not isolated syndromes.<a id=\"xref-ref-7-4\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-7\"><sup>7<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-17-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-17\"><sup>17<\/sup><\/a><sup>\u2013<\/sup><a id=\"xref-ref-19-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-19\"><sup>19<\/sup><\/a>\u00a0Further supporting a diagnostic continuum rather than isolated syndromes,\u00a0<em>WT1<\/em>\u00a0variants were identified in several 46, XY patients with genital malformations with and without WT and\/or nephropathy and in patients with WT without genital malformations and\/or nephropathy.<a id=\"xref-ref-7-5\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-7\"><sup>7<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-11-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-11\"><sup>11<\/sup><\/a><sup>\u2013<\/sup><a id=\"xref-ref-14-2\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-14\"><sup>14<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-20-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-20\"><sup>20<\/sup><\/a><sup>\u2013<\/sup><a id=\"xref-ref-23-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-23\"><sup>23<\/sup><\/a><\/p>\n<p id=\"p-11\">Despite their clear association with genitourinary malformations,\u00a0<em>WT1<\/em>\u00a0variants are an uncommon cause of isolated hypospadias.<a id=\"xref-ref-7-6\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-7\"><sup>7<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-24-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-24\"><sup>24<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-25-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-25\"><sup>25<\/sup><\/a>\u00a0In a pediatric series, 210 male patients with 46, XY DSDs were assessed for genetic alterations and a\u00a0<em>WT1<\/em>\u00a0variant was identified in 7. Two of these patients presented with penoscrotal hypospadias, normal phallus size, bifid scrotum, and unilateral cryptorchidism, abnormalities similar to the ones identified in our case patient except for the presence of cryptorchidism. One patient with a truncating mutation in exon 1 had WT in infancy and normal renal function at age 23. Another patient with a missense mutation in exon 2 had no reported renal abnormalities by age 12. All 7 patients had unilateral or bilateral cryptorchidism, and 6 had associated hypospadias;\u00a0<em>WT1<\/em>\u00a0variants were not identified in any patient with bilaterally descended testes. The authors concluded that newborns with complex hypospadias and unilateral or bilateral cryptorchidism should be evaluated for\u00a0<em>WT1<\/em>\u00a0mutations; in those with severe hypospadias and bilaterally descended testes, however, they proposed that\u00a0<em>WT1<\/em>\u00a0analysis is not warranted.<a id=\"xref-ref-7-7\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-7\"><sup>7<\/sup><\/a><\/p>\n<p id=\"p-12\">In other studies, researchers evaluating patients for\u00a0<em>WT1<\/em>\u00a0variants reported that all patients with a\u00a0<em>WT1<\/em>\u00a0alteration and hypospadias had a history of unilateral or bilateral cryptorchidism.<a id=\"xref-ref-7-8\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-7\"><sup>7<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-10-5\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-10\"><sup>10<\/sup><\/a><sup>,<\/sup><a id=\"xref-ref-26-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-26\"><sup>26<\/sup><\/a>\u00a0Specifically, Lehnhardt et al<a id=\"xref-ref-10-6\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-10\"><sup>10<\/sup><\/a>\u00a0described the phenotypes of 53 individuals with constitutional, heterozygous\u00a0<em>WT1<\/em>\u00a0mutations treated at pediatric nephrology centers in Germany, Austria, and Switzerland and identified 32 male patients with genitourinary malformations. All male patients with hypospadias had unilateral or bilateral cryptorchidism with or without other anomalies. Lehnhardt et al<a id=\"xref-ref-10-7\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-10\"><sup>10<\/sup><\/a>\u00a0noted that only 1 patient in this cohort fit a classic diagnosis for a\u00a0<em>WT1<\/em>\u00a0disorder, supporting previous reports that these syndromes (DDS and FS) are the extremes of a spectrum of disorders.<a id=\"xref-ref-27-1\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-27\"><sup>27<\/sup><\/a>\u00a0Wang et al<a id=\"xref-ref-25-2\" class=\"xref-bibr\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#ref-25\"><sup>25<\/sup><\/a>\u00a0evaluated 90 male patients with hypospadias for mutations in\u00a0<em>SRY<\/em>,\u00a0<em>SOX9<\/em>,\u00a0<em>WT1<\/em>,\u00a0<em>AR<\/em>, and\u00a0<em>SRD5A2<\/em>\u00a0and identified\u00a0<em>WT1<\/em>\u00a0variants in 3 adult patients with hypospadias and no other abnormalities.<\/p>\n<p id=\"p-13\">Despite bilaterally descended testes, multigene panel testing resulted in identification of a\u00a0<em>WT1<\/em>\u00a0variant in our patient. The multigene panel employed was created by an endocrinologist and genetic counselor after review of the current literature for use in cases of atypical genitalia without a clear etiology and broad differential diagnosis. In these situations, multigene panels increase diagnostic yield at a lower cost than sequential, single-gene testing; targeted gene testing; or whole-exome sequencing. Ultimately, identification of a\u00a0<em>WT1<\/em>\u00a0variant prompted screening for and diagnosis of WT. This is significant because earlier diagnoses of WT may result in identification of smaller tumors and the potential for nephron-sparing surgical options.<\/p>\n<p id=\"p-14\">With our case, we add to a small number of cases that can be used to contradict previous suggestions that\u00a0<em>WT1<\/em>\u00a0testing is not indicated for isolated hypospadias without cryptorchidism. Although isolated proximal hypospadias is historically considered an anatomic abnormality, the association with genitourinary malformations (as evidenced above) should prompt consideration of further genetic testing. In light of technological advances and an unclear implication of genetic variants on phenotype, at this time, all patients with genitourinary anomalies should be carefully considered, and the utility of genetic evaluation should be determined on an individual basis. Inevitably, many newly discovered variants may have unclear clinical significance, and because of the rarity of these mutations, creation of national and international databases would be integral to establishing genotype-phenotype correlation.<\/p>\n<\/div>\n<div id=\"ack-1\" class=\"section ack\">\n<h2 class=\"\">Acknowledgment<\/h2>\n<p id=\"p-23\">The authors would like to thank Dr Mariana Cajaiba for providing the pathology images.<\/p>\n<\/div>\n<div id=\"fn-group-1\" class=\"section fn-group\">\n<h2>Footnotes<\/h2>\n<ul>\n<li style=\"list-style-type: none;\">\n<ul class=\"history-list\">\n<li class=\"accepted\"><span class=\"accepted-label\">Accepted\u00a0<\/span>July 31, 2017.<\/li>\n<\/ul>\n<\/li>\n<li id=\"corresp-1\" class=\"corresp\">Address correspondence to Elizabeth Dabrowski, MD, Department of Pediatric Endocrinology, Ann &amp; Robert H. Lurie Children\u2019s Hospital, 225 E. Chicago Ave, Box 54, Chicago, IL 60611. E-mail:\u00a0<span class=\"em-link\"><span class=\"em-addr\"><a href=\"mailto:eadabrowski@gmail.com\">eadabrowski@gmail.com<\/a><\/span><\/span><\/li>\n<li id=\"fn-2\" class=\"fn-financial-disclosure financial-disclosure\">\n<p id=\"p-20\"><strong>FINANCIAL DISCLOSURE:<\/strong>\u00a0The authors have indicated they have no financial relationships relevant to this article to disclose.<\/p>\n<\/li>\n<li id=\"fn-3\" class=\"fn-supported-by supported-by\">\n<p id=\"p-21\"><strong>FUNDING:<\/strong>\u00a0No external funding.<\/p>\n<\/li>\n<li id=\"fn-4\" class=\"fn-conflict conflict\">\n<p id=\"p-22\"><strong>POTENTIAL CONFLICT OF INTEREST:<\/strong>\u00a0The authors have indicated they have no potential conflicts of interest to disclose.<\/p>\n<\/li>\n<\/ul>\n<\/div>\n<div id=\"ref-list-1\" class=\"section ref-list\">\n<h2 class=\"\">References<\/h2>\n<ol class=\"cit-list\">\n<li><a id=\"ref-1\" class=\"rev-xref-ref\" title=\"View reference 1 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-1-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.1\" class=\"cit ref-cit ref-journal\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Lee<\/span>\u00a0<span class=\"cit-name-given-names\">PA<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Nordenstr\u00f6m<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Houk<\/span>\u00a0<span class=\"cit-name-given-names\">CP<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span>;\u00a0<span class=\"cit-auth cit-collab\">Global DSD Update Consortium<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Global disorders of sex development update since 2006: perceptions, approach and care [published correction appears in\u00a0<em>Horm Res Paediatr<\/em>. 2016;85(3):180].<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Horm Res Paediatr<\/abbr>.\u00a0<span class=\"cit-pub-date\">2016<\/span>;<span class=\"cit-vol\">85<\/span>(<span class=\"cit-issue\">3<\/span>):<span class=\"cit-fpage\">158<\/span>\u2013<span class=\"cit-lpage\">180<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>26820577<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=26820577&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-2\" class=\"rev-xref-ref\" title=\"View reference 2 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-2-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.2\" class=\"cit ref-cit ref-journal\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Kim<\/span>\u00a0<span class=\"cit-name-given-names\">KS<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Kim<\/span>\u00a0<span class=\"cit-name-given-names\">J<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Disorders of sex development.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Korean J Urol<\/abbr>.\u00a0<span class=\"cit-pub-date\">2012<\/span>;<span class=\"cit-vol\">53<\/span>(<span class=\"cit-issue\">1<\/span>):<span class=\"cit-fpage\">1<\/span>\u2013<span class=\"cit-lpage\">8<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>22323966<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=22323966&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-3\" class=\"rev-xref-ref\" title=\"View reference 3 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-3-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.3\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1210\/jc.2014-2605\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Baxter<\/span>\u00a0<span class=\"cit-name-given-names\">RM<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Arboleda<\/span>\u00a0<span class=\"cit-name-given-names\">VA<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Lee<\/span>\u00a0<span class=\"cit-name-given-names\">H<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Exome sequencing for the diagnosis of 46,XY disorders of sex development.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">J Clin Endocrinol Metab<\/abbr>.\u00a0<span class=\"cit-pub-date\">2015<\/span>;<span class=\"cit-vol\">100<\/span>(<span class=\"cit-issue\">2<\/span>):<span class=\"cit-fpage\">E333<\/span>\u2013<span class=\"cit-lpage\">E344<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>25383892<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1210\/jc.2014-2605&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=25383892&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-4\" class=\"rev-xref-ref\" title=\"View reference 4 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-4-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.4\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1093\/nar\/gkn665\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Amberger<\/span>\u00a0<span class=\"cit-name-given-names\">J<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Bocchini<\/span>\u00a0<span class=\"cit-name-given-names\">CA<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Scott<\/span>\u00a0<span class=\"cit-name-given-names\">AF<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Hamosh<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">McKusick\u2019s Online Mendelian Inheritance in Man (OMIM).<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Nucleic Acids Res<\/abbr>.\u00a0<span class=\"cit-pub-date\">2009<\/span>;<span class=\"cit-vol\">37<\/span>(<span class=\"cit-issue\">Database issue<\/span>):<span class=\"cit-fpage\">D793<\/span>\u2013<span class=\"cit-lpage\">D796<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>18842627<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1093\/nar\/gkn665&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=18842627&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000261906200138&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li>\n<div id=\"cit-141.Supplement_5.S491.5\" class=\"cit ref-cit ref-journal no-rev-xref\" data-doi=\"10.1093\/nar\/gkt1113\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Landrum<\/span>\u00a0<span class=\"cit-name-given-names\">MJ<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Lee<\/span>\u00a0<span class=\"cit-name-given-names\">JM<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Riley<\/span>\u00a0<span class=\"cit-name-given-names\">GR<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">ClinVar: public archive of relationships among sequence variation and human phenotype.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Nucleic Acids Res<\/abbr>.\u00a0<span class=\"cit-pub-date\">2014<\/span>;<span class=\"cit-vol\">42<\/span>(<span class=\"cit-issue\">Database issue<\/span>):<span class=\"cit-fpage\">D980<\/span>\u2013<span class=\"cit-lpage\">D985<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>24234437<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1093\/nar\/gkt1113&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=24234437&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000331139800144&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-6\" class=\"rev-xref-ref\" title=\"View reference 6 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-6-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.6\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1007\/s00439-013-1358-4\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Stenson<\/span>\u00a0<span class=\"cit-name-given-names\">PD<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Mort<\/span>\u00a0<span class=\"cit-name-given-names\">M<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Ball<\/span>\u00a0<span class=\"cit-name-given-names\">EV<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Shaw<\/span>\u00a0<span class=\"cit-name-given-names\">K<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Phillips<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Cooper<\/span>\u00a0<span class=\"cit-name-given-names\">DN<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">The Human Gene Mutation Database: building a comprehensive mutation repository for clinical and molecular genetics, diagnostic testing and personalized genomic medicine.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Hum Genet<\/abbr>.\u00a0<span class=\"cit-pub-date\">2014<\/span>;<span class=\"cit-vol\">133<\/span>(<span class=\"cit-issue\">1<\/span>):<span class=\"cit-fpage\">1<\/span>\u2013<span class=\"cit-lpage\">9<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>24077912<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1007\/s00439-013-1358-4&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=24077912&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-7\" class=\"rev-xref-ref\" title=\"View reference 7 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-7-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.7\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1210\/jc.2010-2804\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">K\u00f6hler<\/span>\u00a0<span class=\"cit-name-given-names\">B<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Biebermann<\/span>\u00a0<span class=\"cit-name-given-names\">H<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Friedsam<\/span>\u00a0<span class=\"cit-name-given-names\">V<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Analysis of the Wilms\u2019 tumor suppressor gene (WT1) in patients 46,XY disorders of sex development.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">J Clin Endocrinol Metab<\/abbr>.\u00a0<span class=\"cit-pub-date\">2011<\/span>;<span class=\"cit-vol\">96<\/span>(<span class=\"cit-issue\">7<\/span>):<span class=\"cit-fpage\">E1131<\/span>\u2013<span class=\"cit-lpage\">E1136<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>21508141<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1210\/jc.2010-2804&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=21508141&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-8\" class=\"rev-xref-ref\" title=\"View reference 8 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-8-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.8\" class=\"cit ref-cit ref-journal\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Cox<\/span>\u00a0<span class=\"cit-name-given-names\">SG<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Kilborn<\/span>\u00a0<span class=\"cit-name-given-names\">T<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Pillay<\/span>\u00a0<span class=\"cit-name-given-names\">K<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Davidson<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Millar<\/span>\u00a0<span class=\"cit-name-given-names\">AJ<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Magnetic resonance imaging versus histopathology in Wilms tumor and nephroblastomatosis: 3 examples of noncorrelation.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">J Pediatr Hematol Oncol<\/abbr>.\u00a0<span class=\"cit-pub-date\">2014<\/span>;<span class=\"cit-vol\">36<\/span>(<span class=\"cit-issue\">2<\/span>):<span class=\"cit-fpage\">e81<\/span>\u2013<span class=\"cit-lpage\">e84<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>23652879<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=23652879&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-9\" class=\"rev-xref-ref\" title=\"View reference 9 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-9-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.9\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1111\/j.1523-1755.2004.00775.x\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Ruf<\/span>\u00a0<span class=\"cit-name-given-names\">RG<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Schultheiss<\/span>\u00a0<span class=\"cit-name-given-names\">M<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Lichtenberger<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span>;\u00a0<span class=\"cit-auth cit-collab\">APN Study Group<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Prevalence of WT1 mutations in a large cohort of patients with steroid-resistant and steroid-sensitive nephrotic syndrome.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Kidney Int<\/abbr>.\u00a0<span class=\"cit-pub-date\">2004<\/span>;<span class=\"cit-vol\">66<\/span>(<span class=\"cit-issue\">2<\/span>):<span class=\"cit-fpage\">564<\/span>\u2013<span class=\"cit-lpage\">570<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>15253707<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1111\/j.1523-1755.2004.00775.x&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=15253707&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000222578400016&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-10\" class=\"rev-xref-ref\" title=\"View reference 10 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-10-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.10\" class=\"cit ref-cit ref-journal\" data-doi=\"10.2215\/CJN.10141014\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Lehnhardt<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Karnatz<\/span>\u00a0<span class=\"cit-name-given-names\">C<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Ahlenstiel-Grunow<\/span>\u00a0<span class=\"cit-name-given-names\">T<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Clinical and molecular characterization of patients with heterozygous mutations in Wilms tumor suppressor gene 1.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Clin J Am Soc Nephrol<\/abbr>.\u00a0<span class=\"cit-pub-date\">2015<\/span>;<span class=\"cit-vol\">10<\/span>(<span class=\"cit-issue\">5<\/span>):<span class=\"cit-fpage\">825<\/span>\u2013<span class=\"cit-lpage\">831<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>25818337<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-ijlink\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6ODoiY2xpbmphc24iO3M6NToicmVzaWQiO3M6ODoiMTAvNS84MjUiO3M6NDoiYXRvbSI7czozODoiL3BlZGlhdHJpY3MvMTQxL1N1cHBsZW1lbnRfNS9TNDkxLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==\"><span class=\"cit-reflinks-abstract\">Abstract<\/span><span class=\"cit-sep cit-reflinks-variant-name-sep\">\/<\/span><span class=\"cit-reflinks-full-text\"><span class=\"free-full-text\">FREE\u00a0<\/span>Full Text<\/span><\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-11\" class=\"rev-xref-ref\" title=\"View reference 11 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-11-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.11\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1093\/nar\/26.1.271\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Jeanpierre<\/span>\u00a0<span class=\"cit-name-given-names\">C<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">B\u00e9roud<\/span>\u00a0<span class=\"cit-name-given-names\">C<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Niaudet<\/span>\u00a0<span class=\"cit-name-given-names\">P<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Junien<\/span>\u00a0<span class=\"cit-name-given-names\">C<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Software and database for the analysis of mutations in the human WT1 gene.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Nucleic Acids Res<\/abbr>.\u00a0<span class=\"cit-pub-date\">1998<\/span>;<span class=\"cit-vol\">26<\/span>(<span class=\"cit-issue\">1<\/span>):<span class=\"cit-fpage\">271<\/span>\u2013<span class=\"cit-lpage\">274<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>9399851<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1093\/nar\/26.1.271&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=9399851&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000071778900064&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li>\n<div id=\"cit-141.Supplement_5.S491.12\" class=\"cit ref-cit ref-journal no-rev-xref\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Regev<\/span>\u00a0<span class=\"cit-name-given-names\">M<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Kirk<\/span>\u00a0<span class=\"cit-name-given-names\">R<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Mashevich<\/span>\u00a0<span class=\"cit-name-given-names\">M<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Bistritzer<\/span>\u00a0<span class=\"cit-name-given-names\">Z<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Reish<\/span>\u00a0<span class=\"cit-name-given-names\">O<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Vertical transmission of a mutation in exon 1 of the WT1 gene: lessons for genetic counseling.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Am J Med Genet A<\/abbr>.\u00a0<span class=\"cit-pub-date\">2008<\/span>;<span class=\"cit-vol\">146A<\/span>(<span class=\"cit-issue\">18<\/span>):<span class=\"cit-fpage\">2332<\/span>\u2013<span class=\"cit-lpage\">2336<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>18688870<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=18688870&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-13\" class=\"rev-xref-ref\" title=\"View reference 13 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-13-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.13\" class=\"cit ref-cit ref-journal\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Royer-Pokora<\/span>\u00a0<span class=\"cit-name-given-names\">B<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Beier<\/span>\u00a0<span class=\"cit-name-given-names\">M<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Henzler<\/span>\u00a0<span class=\"cit-name-given-names\">M<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Twenty-four new cases of WT1 germline mutations and review of the literature: genotype\/phenotype correlations for Wilms tumor development.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Am J Med Genet A<\/abbr>.\u00a0<span class=\"cit-pub-date\">2004<\/span>;<span class=\"cit-vol\">127A<\/span>(<span class=\"cit-issue\">3<\/span>):<span class=\"cit-fpage\">249<\/span>\u2013<span class=\"cit-lpage\">257<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>15150775<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=15150775&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-14\" class=\"rev-xref-ref\" title=\"View reference 14 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-14-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.14\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1073\/pnas.94.8.3972\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Schumacher<\/span>\u00a0<span class=\"cit-name-given-names\">V<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Schneider<\/span>\u00a0<span class=\"cit-name-given-names\">S<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Figge<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Correlation of germ-line mutations and two-hit inactivation of the WT1 gene with Wilms tumors of stromal-predominant histology.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Proc Natl Acad Sci USA<\/abbr>.\u00a0<span class=\"cit-pub-date\">1997<\/span>;<span class=\"cit-vol\">94<\/span>(<span class=\"cit-issue\">8<\/span>):<span class=\"cit-fpage\">3972<\/span>\u2013<span class=\"cit-lpage\">3977<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>9108089<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-ijlink\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6NDoicG5hcyI7czo1OiJyZXNpZCI7czo5OiI5NC84LzM5NzIiO3M6NDoiYXRvbSI7czozODoiL3BlZGlhdHJpY3MvMTQxL1N1cHBsZW1lbnRfNS9TNDkxLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==\"><span class=\"cit-reflinks-abstract\">Abstract<\/span><span class=\"cit-sep cit-reflinks-variant-name-sep\">\/<\/span><span class=\"cit-reflinks-full-text\"><span class=\"free-full-text\">FREE\u00a0<\/span>Full Text<\/span><\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-15\" class=\"rev-xref-ref\" title=\"View reference 15 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-15-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.15\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1016\/S0022-3476(85)80076-7\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Eddy<\/span>\u00a0<span class=\"cit-name-given-names\">AA<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Mauer<\/span>\u00a0<span class=\"cit-name-given-names\">SM<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Pseudohermaphroditism, glomerulopathy, and Wilms tumor (Drash syndrome): frequency in end-stage renal failure.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">J Pediatr<\/abbr>.\u00a0<span class=\"cit-pub-date\">1985<\/span>;<span class=\"cit-vol\">106<\/span>(<span class=\"cit-issue\">4<\/span>):<span class=\"cit-fpage\">584<\/span>\u2013<span class=\"cit-lpage\">587<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>2984395<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1016\/S0022-3476(85)80076-7&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=2984395&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=A1985AFT0900009&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-16\" class=\"rev-xref-ref\" title=\"View reference 16 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-16-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.16\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1136\/jmg.31.6.471\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Mueller<\/span>\u00a0<span class=\"cit-name-given-names\">RF<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">The Denys-Drash syndrome.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">J Med Genet<\/abbr>.\u00a0<span class=\"cit-pub-date\">1994<\/span>;<span class=\"cit-vol\">31<\/span>(<span class=\"cit-issue\">6<\/span>):<span class=\"cit-fpage\">471<\/span>\u2013<span class=\"cit-lpage\">477<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>8071974<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-ijlink\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6MzoiUERGIjtzOjExOiJqb3VybmFsQ29kZSI7czo5OiJqbWVkZ2VuZXQiO3M6NToicmVzaWQiO3M6ODoiMzEvNi80NzEiO3M6NDoiYXRvbSI7czozODoiL3BlZGlhdHJpY3MvMTQxL1N1cHBsZW1lbnRfNS9TNDkxLmF0b20iO31zOjg6ImZyYWdtZW50IjtzOjA6IiI7fQ==\"><span class=\"cit-reflinks-full-text\"><span class=\"free-full-text\">FREE\u00a0<\/span>Full Text<\/span><\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-17\" class=\"rev-xref-ref\" title=\"View reference 17 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-17-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.17\" class=\"cit ref-cit ref-journal\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Finken<\/span>\u00a0<span class=\"cit-name-given-names\">MJ<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Hendriks<\/span>\u00a0<span class=\"cit-name-given-names\">YM<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">van der Voorn<\/span>\u00a0<span class=\"cit-name-given-names\">JP<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Veening<\/span>\u00a0<span class=\"cit-name-given-names\">MA<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Lombardi<\/span>\u00a0<span class=\"cit-name-given-names\">MP<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Rotteveel<\/span>\u00a0<span class=\"cit-name-given-names\">J<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">WT1 deletion leading to severe 46,XY gonadal dysgenesis, Wilms tumor and gonadoblastoma: case report.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Horm Res Paediatr<\/abbr>.\u00a0<span class=\"cit-pub-date\">2015<\/span>;<span class=\"cit-vol\">83<\/span>(<span class=\"cit-issue\">3<\/span>):<span class=\"cit-fpage\">211<\/span>\u2013<span class=\"cit-lpage\">216<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>25613702<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=25613702&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li>\n<div id=\"cit-141.Supplement_5.S491.18\" class=\"cit ref-cit ref-journal no-rev-xref\" data-doi=\"10.1046\/j.1365-2265.2000.00980.x\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Koziell<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Charmandari<\/span>\u00a0<span class=\"cit-name-given-names\">E<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Hindmarsh<\/span>\u00a0<span class=\"cit-name-given-names\">PC<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Rees<\/span>\u00a0<span class=\"cit-name-given-names\">L<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Scambler<\/span>\u00a0<span class=\"cit-name-given-names\">P<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Brook<\/span>\u00a0<span class=\"cit-name-given-names\">CG<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Frasier syndrome, part of the Denys Drash continuum or simply a WT1 gene associated disorder of intersex and nephropathy?<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Clin Endocrinol (Oxf)<\/abbr>.\u00a0<span class=\"cit-pub-date\">2000<\/span>;<span class=\"cit-vol\">52<\/span>(<span class=\"cit-issue\">4<\/span>):<span class=\"cit-fpage\">519<\/span>\u2013<span class=\"cit-lpage\">524<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>10762296<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1046\/j.1365-2265.2000.00980.x&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10762296&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-19\" class=\"rev-xref-ref\" title=\"View reference 19 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-19-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.19\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1002\/ijc.25067\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Breslow<\/span>\u00a0<span class=\"cit-name-given-names\">NE<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Lange<\/span>\u00a0<span class=\"cit-name-given-names\">JM<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Friedman<\/span>\u00a0<span class=\"cit-name-given-names\">DL<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Secondary malignant neoplasms after Wilms tumor: an international collaborative study.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Int J Cancer<\/abbr>.\u00a0<span class=\"cit-pub-date\">2010<\/span>;<span class=\"cit-vol\">127<\/span>(<span class=\"cit-issue\">3<\/span>):<span class=\"cit-fpage\">657<\/span>\u2013<span class=\"cit-lpage\">666<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>19950224<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1002\/ijc.25067&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=19950224&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000279131300017&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-20\" class=\"rev-xref-ref\" title=\"View reference 20 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-20-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.20\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1530\/eje.0.1500825\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">K\u00f6hler<\/span>\u00a0<span class=\"cit-name-given-names\">B<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Pienkowski<\/span>\u00a0<span class=\"cit-name-given-names\">C<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Audran<\/span>\u00a0<span class=\"cit-name-given-names\">F<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">An N-terminal WT1 mutation (P181S) in an XY patient with ambiguous genitalia, normal testosterone production, absence of kidney disease and associated heart defect: enlarging the phenotypic spectrum of WT1 defects.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Eur J Endocrinol<\/abbr>.\u00a0<span class=\"cit-pub-date\">2004<\/span>;<span class=\"cit-vol\">150<\/span>(<span class=\"cit-issue\">6<\/span>):<span class=\"cit-fpage\">825<\/span>\u2013<span class=\"cit-lpage\">830<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>15191353<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-ijlink\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiZWplIjtzOjU6InJlc2lkIjtzOjk6IjE1MC82LzgyNSI7czo0OiJhdG9tIjtzOjM4OiIvcGVkaWF0cmljcy8xNDEvU3VwcGxlbWVudF81L1M0OTEuYXRvbSI7fXM6ODoiZnJhZ21lbnQiO3M6MDoiIjt9\"><span class=\"cit-reflinks-abstract\">Abstract<\/span><\/a><\/div>\n<\/div>\n<\/li>\n<li>\n<div id=\"cit-141.Supplement_5.S491.21\" class=\"cit ref-cit ref-journal no-rev-xref\" data-doi=\"10.1067\/mpd.2001.112512\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">K\u00f6hler<\/span>\u00a0<span class=\"cit-name-given-names\">B<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Schumacher<\/span>\u00a0<span class=\"cit-name-given-names\">V<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">l\u2019Allemand<\/span>\u00a0<span class=\"cit-name-given-names\">D<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Royer-Pokora<\/span>\u00a0<span class=\"cit-name-given-names\">B<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Gr\u00fcters<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Germline Wilms tumor suppressor gene (WT1) mutation leading to isolated genital malformation without Wilms tumor or nephropathy.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">J Pediatr<\/abbr>.\u00a0<span class=\"cit-pub-date\">2001<\/span>;<span class=\"cit-vol\">138<\/span>(<span class=\"cit-issue\">3<\/span>):<span class=\"cit-fpage\">421<\/span>\u2013<span class=\"cit-lpage\">424<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>11241055<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1067\/mpd.2001.112512&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=11241055&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000167591200025&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li>\n<div id=\"cit-141.Supplement_5.S491.22\" class=\"cit ref-cit ref-journal no-rev-xref\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">K\u00f6hler<\/span>\u00a0<span class=\"cit-name-given-names\">B<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Schumacher<\/span>\u00a0<span class=\"cit-name-given-names\">V<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Schulte-Overberg<\/span>\u00a0<span class=\"cit-name-given-names\">U<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Bilateral Wilms tumor in a boy with severe hypospadias and cryptochidism due to a heterozygous mutation in the WT1 gene.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Pediatr Res<\/abbr>.\u00a0<span class=\"cit-pub-date\">1999<\/span>;<span class=\"cit-vol\">45<\/span>(<span class=\"cit-issue\">2<\/span>):<span class=\"cit-fpage\">187<\/span>\u2013<span class=\"cit-lpage\">190<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>10022588<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10022588&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000078411800005&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-23\" class=\"rev-xref-ref\" title=\"View reference 23 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-23-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.23\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1200\/JCO.2004.02.136\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Little<\/span>\u00a0<span class=\"cit-name-given-names\">SE<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Hanks<\/span>\u00a0<span class=\"cit-name-given-names\">SP<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">King-Underwood<\/span>\u00a0<span class=\"cit-name-given-names\">L<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Frequency and heritability of WT1 mutations in nonsyndromic Wilms\u2019 tumor patients: a UK Children\u2019s Cancer Study Group Study.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">J Clin Oncol<\/abbr>.\u00a0<span class=\"cit-pub-date\">2004<\/span>;<span class=\"cit-vol\">22<\/span>(<span class=\"cit-issue\">20<\/span>):<span class=\"cit-fpage\">4140<\/span>\u2013<span class=\"cit-lpage\">4146<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>15483024<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-ijlink\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/ijlink\/YTozOntzOjQ6InBhdGgiO3M6MTQ6Ii9sb29rdXAvaWpsaW5rIjtzOjU6InF1ZXJ5IjthOjQ6e3M6ODoibGlua1R5cGUiO3M6NDoiQUJTVCI7czoxMToiam91cm5hbENvZGUiO3M6MzoiamNvIjtzOjU6InJlc2lkIjtzOjEwOiIyMi8yMC80MTQwIjtzOjQ6ImF0b20iO3M6Mzg6Ii9wZWRpYXRyaWNzLzE0MS9TdXBwbGVtZW50XzUvUzQ5MS5hdG9tIjt9czo4OiJmcmFnbWVudCI7czowOiIiO30=\"><span class=\"cit-reflinks-abstract\">Abstract<\/span><span class=\"cit-sep cit-reflinks-variant-name-sep\">\/<\/span><span class=\"cit-reflinks-full-text\"><span class=\"free-full-text\">FREE\u00a0<\/span>Full Text<\/span><\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-24\" class=\"rev-xref-ref\" title=\"View reference 24 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-24-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.24\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1093\/humupd\/dms002\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">van der Zanden<\/span>\u00a0<span class=\"cit-name-given-names\">LF<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">van Rooij<\/span>\u00a0<span class=\"cit-name-given-names\">IA<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Feitz<\/span>\u00a0<span class=\"cit-name-given-names\">WF<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Franke<\/span>\u00a0<span class=\"cit-name-given-names\">B<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Knoers<\/span>\u00a0<span class=\"cit-name-given-names\">NV<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Roeleveld<\/span>\u00a0<span class=\"cit-name-given-names\">N<\/span><\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Aetiology of hypospadias: a systematic review of genes and environment.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Hum Reprod Update<\/abbr>.\u00a0<span class=\"cit-pub-date\">2012<\/span>;<span class=\"cit-vol\">18<\/span>(<span class=\"cit-issue\">3<\/span>):<span class=\"cit-fpage\">260<\/span>\u2013<span class=\"cit-lpage\">283<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>22371315<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1093\/humupd\/dms002&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=22371315&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000303162500004&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-25\" class=\"rev-xref-ref\" title=\"View reference 25 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-25-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.25\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1038\/sj.ejhg.5201232\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Wang<\/span>\u00a0<span class=\"cit-name-given-names\">Y<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Li<\/span>\u00a0<span class=\"cit-name-given-names\">Q<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Xu<\/span>\u00a0<span class=\"cit-name-given-names\">J<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Mutation analysis of five candidate genes in Chinese patients with hypospadias.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Eur J Hum Genet<\/abbr>.\u00a0<span class=\"cit-pub-date\">2004<\/span>;<span class=\"cit-vol\">12<\/span>(<span class=\"cit-issue\">9<\/span>):<span class=\"cit-fpage\">706<\/span>\u2013<span class=\"cit-lpage\">712<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>15266301<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1038\/sj.ejhg.5201232&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=15266301&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000223403900004&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-26\" class=\"rev-xref-ref\" title=\"View reference 26 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-26-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.26\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1007\/s002400050088\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Nordenskj\u00f6ld<\/span>\u00a0<span class=\"cit-name-given-names\">A<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Friedman<\/span>\u00a0<span class=\"cit-name-given-names\">E<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Tapper-Persson<\/span>\u00a0<span class=\"cit-name-given-names\">M<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">Screening for mutations in candidate genes for hypospadias.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">Urol Res<\/abbr>.\u00a0<span class=\"cit-pub-date\">1999<\/span>;<span class=\"cit-vol\">27<\/span>(<span class=\"cit-issue\">1<\/span>):<span class=\"cit-fpage\">49<\/span>\u2013<span class=\"cit-lpage\">55<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>10092153<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1007\/s002400050088&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10092153&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000078891100008&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<li><a id=\"ref-27\" class=\"rev-xref-ref\" title=\"View reference 27 in text\" href=\"http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long#xref-ref-27-1\">\u21b5<\/a>\n<div id=\"cit-141.Supplement_5.S491.27\" class=\"cit ref-cit ref-journal\" data-doi=\"10.1210\/jc.87.6.2500\">\n<div class=\"cit-metadata\">\n<ol class=\"cit-auth-list\">\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Melo<\/span>\u00a0<span class=\"cit-name-given-names\">KF<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Martin<\/span>\u00a0<span class=\"cit-name-given-names\">RM<\/span><\/span>,<\/li>\n<li><span class=\"cit-auth\"><span class=\"cit-name-surname\">Costa<\/span>\u00a0<span class=\"cit-name-given-names\">EM<\/span><\/span>,\u00a0<span class=\"cit-etal\">et al<\/span><\/li>\n<\/ol>\n<p><cite>.\u00a0<span class=\"cit-article-title\">An unusual phenotype of Frasier syndrome due to IVS9 +4C&gt;T mutation in the WT1 gene: predominantly male ambiguous genitalia and absence of gonadal dysgenesis.<\/span>\u00a0<abbr class=\"cit-jnl-abbrev\">J Clin Endocrinol Metab<\/abbr>.\u00a0<span class=\"cit-pub-date\">2002<\/span>;<span class=\"cit-vol\">87<\/span>(<span class=\"cit-issue\">6<\/span>):<span class=\"cit-fpage\">2500<\/span>\u2013<span class=\"cit-lpage\">2505<\/span><span class=\"cit-pub-id cit-pub-id-pmid\"><span class=\"cit-pub-id-scheme-pmid\">pmid:<\/span>12050205<\/span><\/cite><\/p>\n<\/div>\n<div class=\"cit-extra\"><a class=\"cit-ref-sprinkles cit-ref-sprinkles-doi cit-ref-sprinkles-crossref\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=10.1210\/jc.87.6.2500&amp;link_type=DOI\">CrossRef<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-medline\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=12050205&amp;link_type=MED&amp;atom=%2Fpediatrics%2F141%2FSupplement_5%2FS491.atom\">PubMed<\/a><a class=\"cit-ref-sprinkles cit-ref-sprinkles-newisilink cit-ref-sprinkles-webofscience\" href=\"http:\/\/pediatrics.aappublications.org\/lookup\/external-ref?access_num=000176241000014&amp;link_type=ISI\">Web of Science<\/a><\/div>\n<\/div>\n<\/li>\n<\/ol>\n<\/div>\n<ul class=\"copyright-statement\">\n<li id=\"copyright-statement-1\" class=\"fn\">Copyright \u00a9 2018 by the American Academy of Pediatrics<\/li>\n<\/ul>\n<p><em><strong>\u0414\u0436\u0435\u0440\u0435\u043b\u043e<\/strong><\/em>:\u00a0http:\/\/pediatrics.aappublications.org\/content\/141\/Supplement_5\/S491.long<\/p>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"<p>Pediatrics April 2018, VOLUME 141 \/ ISSUE Supplement 5 From the American Academy of Pediatrics Case Report Proximal Hypospadias and a Novel\u00a0WT1\u00a0Variant: When Should Genetic Testing Be Considered? Elizabeth Dabrowski,\u00a0Amy E. Armstrong,\u00a0Elizabeth Leeth,\u00a0Emilie Johnson,\u00a0Earl Cheng,\u00a0Yasmin Gosiengfiao,\u00a0Courtney Finlayson Article Figures &amp; Data Info &amp; Metrics Comments Download PDF Abstract We present a case of an infant [&hellip;]<\/p>\n","protected":false},"author":1,"featured_media":0,"comment_status":"open","ping_status":"open","sticky":false,"template":"","format":"standard","meta":[],"categories":[9],"tags":[724,725],"_links":{"self":[{"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=\/wp\/v2\/posts\/2011"}],"collection":[{"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=\/wp\/v2\/posts"}],"about":[{"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=\/wp\/v2\/users\/1"}],"replies":[{"embeddable":true,"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=%2Fwp%2Fv2%2Fcomments&post=2011"}],"version-history":[{"count":2,"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=\/wp\/v2\/posts\/2011\/revisions"}],"predecessor-version":[{"id":2013,"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=\/wp\/v2\/posts\/2011\/revisions\/2013"}],"wp:attachment":[{"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=%2Fwp%2Fv2%2Fmedia&parent=2011"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=%2Fwp%2Fv2%2Fcategories&post=2011"},{"taxonomy":"post_tag","embeddable":true,"href":"http:\/\/www.drshevchuk.com.ua\/index.php?rest_route=%2Fwp%2Fv2%2Ftags&post=2011"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}