title: A familial WT1 mutation associated with incomplete Denys-Drash syndrome.
abstract: Denys-Drash syndrome (DDS) is a rare disorder characterized by nephropathy, male pseudohermaphroditism, and wilms tumor. Cases are thought to arise sporadically through a de novo mutation in the wilms tumor suppressor gene (WT1), which encodes a zinc finger protein that not only acts as a tumor suppressor but is essential for normal gonadogenesis, nephrogenesis, and development of the urogenital tract. In this report, we describe a family with the well-known missense mutation in exon 9 of the WT1 gene, 1180C>T (R394W), causing incomplete DDS and no symptoms in their father. The proband, a boy with 46, XY karyotype, was born with ambiguous genitalia, penoscrotal hypospadias, and bilateral inguinal hernias. At 2 years of age, he has proteinuria and diffuse mesangial sclerosis, but no wilms tumor has been detected. The elder sister of the proband, at 3 years of age, has normal genitalia, proteinuria, focal mesangial sclerosis but no wilms tumor. The WT1 mutation was detected in both patients, who have suspected DDS, and their father, who is phenotypically normal.
  
  
  CONCLUSIONS
  This case is unusual in that the 1180C>T mutation, which has been found in approximately 50 % of patients with complete DDS, has been inherited and is causing mild or no symptoms of DDS.
authors.affiliation: Department of Nephrology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing, 210008, Jiangsu Province, China.
authors.forename: Chunhua
authors.initials: C
authors.lastname: Zhu
authors.forename: Fei
authors.initials: F
authors.lastname: Zhao
authors.forename: Weizhen
authors.initials: W
authors.lastname: Zhang
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wu
authors.forename: Ying
authors.initials: Y
authors.lastname: Chen
authors.forename: Guixia
authors.initials: G
authors.lastname: Ding
authors.forename: Aihua
authors.initials: A
authors.lastname: Zhang
authors.forename: Songming
authors.initials: S
authors.lastname: Huang
mesh_terms: D002675:Child, Preschool; D030321:Denys-Drash Syndrome / Q000235:genetics*; D012734:Disorders of Sex Development / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D025721:WT1 Proteins; C583751:WT1 protein, human