A Newly Identified Mutation in the WT1 Gene in Denys-Drash Syndrome

Abstract

Denys-Drash syndrome (DDS) is a rare autosomal dominant disorder characterized by genital abnormalities, nephropathy, and Wilms’ tumor (WT), typically caused by heterozygous mutations in the Wilms’ tumor suppressor 1 (WT1) gene. Here, a 2-year-old male admitted with fever and abdominal pain was presented. Physical examination revealed ambiguous genitalia and a palpable abdominal mass. Imaging identified a heterogeneous mass in the left kidney, consistent with WT. Genetic analysis detected a novel heterozygous frameshift mutation in exon 8 of the WT1 gene [p.H245Tfs*2 (c.1393delC)]. WT is the most common renal tumor in children and is frequently associated with WT1 gene mutations in DDS. Given the early onset and severity of symptoms, early genetic screening for WT1 gene mutations should be considered in patients admitted with ambiguous genitalia and nephrotic syndrome. This case contributes to the understanding of WT1 gene mutations and highlights the importance of molecular analysis in children with genitourinary anomalies.

Keywords

• Ambiguous genitalia
• Denys-Drash Syndrome
• WT1 gene

Denys-Drash Sendromunda WT1 Geninde Yeni Tanımlanan Bir Mutasyon

Abstract

Denys-Drash sendromu (DDS), genital anormallikler, nefropati ve Wilms tümörü (WT) ile karakterize, tipik olarak Wilms tümör baskılayıcı 1 (WT1) genindeki heterozigot mutasyonların neden olduğu nadir görülen otozomal dominant bir hastalıktır. Bu yazıda ateş ve karın ağrısı ile başvuran 2 yaşında bir erkek hasta sunulmuştur. Fizik muayenede belirsiz genital organlar ve karında ele gelen bir kitle saptandı. Görüntülemede sol böbrekte WT ile uyumlu heterojen bir kitle tespit edildi. Genetik analizde WT1 geninin 8. ekzonunda yeni bir heterozigot çerçeve kayması mutasyonu tespit edildi [p.H245Tfs*2 (c.1393delC)]. WT çocuklarda en sık görülen böbrek tümörüdür ve DDS'de sıklıkla WT1 gen mutasyonları ile ilişkilidir. Semptomların erken başlangıcı ve ciddiyeti göz önüne alındığında, belirsiz genital organlar ve nefrotik sendrom ile başvuran hastalarda WT1 gen mutasyonları için erken genetik tarama düşünülmelidir. Bu vaka, WT1 gen mutasyonlarının anlaşılmasına katkıda bulunmakta ve genitoüriner anomalileri olan çocuklarda moleküler analizin önemini vurgulamaktadır.

Keywords

• Ambigus genitalya
• Denys-Drash sendromu
• WT1 geni

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