The same mutation affecting the splicing of WT1 gene is present on Frasier syndrome patients with or without Wilms' tumor
✍ Scribed by Angela S. Barbosa; Charalambos G. Hadjiathanasiou; Charalambos Theodoridis; Astéroula Papathanasiou; Attila Tar; Miklós Merksz; Borbála Györvári; Charles Sultan; Robert Dumas; Francis Jaubert; Patrick Niaudet; Carlos A. Moreira-Filho; Corinne Cotinot; Marc Fellous
- Publisher
- John Wiley and Sons
- Year
- 1999
- Tongue
- English
- Weight
- 464 KB
- Volume
- 13
- Category
- Article
- ISSN
- 1059-7794
No coin nor oath required. For personal study only.
✦ Synopsis
Communicated by Michel Goossens
Denys
-Drash and Frasier syndromes are rare human disorders that associate nephropathy with gonadal and genital abnormalities. In DDS there is a predisposition to Wilms tumor. Heterozygous point mutations in the Wilms tumor, type1 gene (WT1), particularly those altering the zinc finger (ZF) encoding exons, have been reported in most DDS patients, while mutations in intron 9 of the same gene cause FS. This paper describes two cases of DDS, one FS and one patient with Wilms tumor and intersex genitalia, in which mutations were searched by sequencing the exons 8 and 9 of WT1 gene. Patient 1 carried a missense point mutation in exon 8 (ZF2), converting a CGA-Arg codon to a TGA-stop codon. Patient 2 presented a single nucleotide deletion within exon 9 (ZF3) introducing a premature chain termination at codon 398. Patients 3 and 4 had a C®T transition at position +4 of the second alternative splice donor site of exon 9 (this mutation was detected in peripheral blood and in tumor derived DNA of patient 3). However, patient 3 had previously developed a Wilms tumor. This is the first case of Wilms tumor development in a phenotypically and genetically confirmed case of FS. Hum Mutat 13:146153, 1999.