Genetic analysis of two female patients with incomplete Denys-Drash syndrome

Citation
S. Ohta et al., Genetic analysis of two female patients with incomplete Denys-Drash syndrome, ENDOCR J, 47(6), 2000, pp. 683-687
Citations number
16
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
ENDOCRINE JOURNAL
ISSN journal
0918-8959 → ACNP
Volume
47
Issue
6
Year of publication
2000
Pages
683 - 687
Database
ISI
SICI code
0918-8959(200012)47:6<683:GAOTFP>2.0.ZU;2-C
Abstract
Denys-Drash syndrome (DDS) is characterized by genital anomaly, early onset nephropathy and high risk for developing Wilms' tumor (WT). Recently, muta tions in exon 8 or 9 of the Wilms' tumor suppressor gene (WT1) have been fo und 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 pol ymerase-chain reaction (PCR) and direct sequencing. The patients were accom panied 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 P CR product was performed using an automatic DNA sequencer. Two heterozygous missense mutations were found in these patients, including a missense muta tion in exon 9 at codon 388 replacing the wild-type Cys with Phe, and a pre viously described mutation in exon 9 at codon 398 replacing the wild-type L eu with Pro. Cys388Phe is a novel mutation in the WT1 gene in the DDS. Thes e cases are considered to be "incomplete DDS" with nephropathy and Wilms' t umor and without genital anomaly, the validity of which has been confirmed by mutation analysis.