Genetic Analysis of Two Female Patients with Incomplete Denys-Drash Syndrome

Endocrine Journal

HIROSHI SHIRAGA³  HIDEKI FUSE¹  SHOICHIRO OHTA¹  TETSUO OZAWA² 

[1] Department of Urology, Faculty of Medicine, Toyama Medical and Pharmaceutical University;Department of Clinical Laboratory Medicine, Faculty of Medicine, Toyama Medical and Pharmaceutical University;Department of Pediatric Nephrology, Tokyo Women's Medical University

关键词: WT1;    Denys-Drash syndrome;    Renal failure;    Genitourinary abnormality;   

DOI  :  10.1507/endocrj.47.683

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(16)Cited-By(1)Denys-Drash syndrome (DDS) is characterized by genital anomaly, early onset nephropathy and high risk for developing Wilms' tumor (WT). Recently, mutations in exon 8 or 9 of the Wilms' tumor suppressor gene (WT1) have been found in the majority of DDS patients studied. We analyzed these two exons of the WT1 gene in genomic DNA from two female patients with DDS by using polymerase-chain reaction (PCR) and direct sequencing. The patients were accompanied with normal external genitalia, early onset renal failure between 6 and 12 months of age, and unilateral Wilms' tumor. Genomic DNA was isolated from peripheral blood leucocytes of the patients. Amplification of exons 8 and 9 of the WT1 gene by PCR was performed, and direct sequencing of the PCR product was performed using an automatic DNA sequencer. Two heterozygous missense mutations were found in these patients, including a missense mutation in exon 9 at codon 388 replacing the wild-type Cys with Phe, and a previously described mutation in exon 9 at codon 398 replacing the wild-type Leu with Pro. Cys388Phe is a novel mutation in the WT1 gene in the DDS. These cases are considered to be “incomplete DDS” with nephropathy and Wilms' tumor and without genital anomaly, the validity of which has been confirmed by mutation analysis.

【 授权许可】

Unknown