Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome?
AUTOR(ES)
Kikuchi, H
RESUMO
The WT1 gene, one of the genes responsible for Wilms tumour, is thought to play a crucial role in the development of the kidneys and gonads. This gene encodes four protein isoforms resulting from two alternative splicing sites, one of which involves inclusion or exclusion of lysine, threonine, and serine (KTS) between the third and fourth zinc finger domains. WT1 is virtually always mutationally inactivated in patients with Denys-Drash syndrome. We analysed WT1 in eight patients who had been diagnosed as having this syndrome, and identified five previously unknown mutations affecting splicing donor sites of intron 9. These mutations affect alternative splicing. The isoforms retaining KTS are not produced. The clinical features of the patients with these intronic mutations were consistent with those of Frasier syndrome, characterised by a more slowly progressive nephropathy than Denys-Drash syndrome, associated streak gonads, and no Wilms tumour development. Our results indicate that WT1 isoforms, including/excluding KTS, have different functions in tumorigenesis and organogenesis of the kidneys and gonads.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1051186Documentos Relacionados
- WT1 mutations in T-ALL
- A Mammal-Specific Exon of WT1 Is Not Required for Development or Fertility
- Homozygous somatic Wt1 point mutations in sporadic unilateral Wilms tumor.
- Software and database for the analysis of mutations in the human WT1 gene.
- Zinc finger point mutations within the WT1 gene in Wilms tumor patients.