title: Clinical pictures and novel mutations of WT1-associated Denys-Drash syndrome in two Chinese children.
abstract: Denys-Drash syndrome (DDS) is characterized by early onset of nephropathy, genitalia malformation, and Wilms' tumor, where WT1 is the gene that is mutated in most patients. We report two de novo mutations in WT1 found in two Chinese DDS children. Patient 1 was a boy with complete DDS who was presented with progressive nephropathy, unilateral Wilms' tumor, bilateral cryptorchidism, and renal histology showing diffuse mesangial sclerosis (DMS). When the patient was 24 months old, a liver ultrasound showed multiple nodules, and the patient died of pneumonia 1 month later. The de novo novel mutation, c.1130A>T (p.His377Leu), was identified; the mutation replaces histidine with leucine in the zinc finger (Znf) structure and is predicted to change the local spatial structure of the protein. Patient 2 had 46 XX with incomplete DDS and presented with normal genitalia, proteinuria, unilateral Wilms' tumor with renal pedicle lymph node metastasis, and renal histology showing DMS. Her renal function remains normal after 48 months. A de novo mutation, c.1168C>T (p.Arg390Term), was identified; it truncates 60 amino acids at the C terminus, and it is predicted to result in loss of the DNA-binding capacities of the WT1 protein.
authors.affiliation: Department of Paediatrics, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, PR China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yue
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Pei
authors.forename: Liangzhong
authors.initials: L
authors.lastname: Sun
authors.forename: Weijun
authors.initials: W
authors.lastname: Huang
authors.forename: Han
authors.initials: H
authors.lastname: Huang
authors.forename: Bin
authors.initials: B
authors.lastname: Hu
authors.forename: Juan
authors.initials: J
authors.lastname: Yang
authors.forename: Xiaoyun
authors.initials: X
authors.lastname: Jiang
authors.forename: Ying
authors.initials: Y
authors.lastname: Mo
authors.forename: Shumei
authors.initials: S
authors.lastname: Chen
authors.forename: Kar Neng
authors.initials: KN
authors.lastname: Lai
authors.forename: Yiming
authors.initials: Y
authors.lastname: Wang
mesh_terms: D001707:Biopsy, Needle; D017024:Chemotherapy, Adjuvant; D002675:Child, Preschool; D002681:China; D030321:Denys-Drash Syndrome / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D017809:Fatal Outcome; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D007680:Kidney Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000601:surgery; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D009392:Nephrectomy / Q000379:methods; D018570:Risk Assessment; D016896:Treatment Outcome; D025721:WT1 Proteins / Q000235:genetics*
chemical_list: D025721:WT1 Proteins