Do intronic mutations affecting splicing of WT1 exon 9 cause Frasier syndrome?

Haruhito Kikuchi, Ayako Takata, Yoshikiyo Akasaka, Ryuji Fukuzawa, Hiroshi Yoneyama, Yoshihiro Kurosawa, Masataka Honda, Yasunori Kamiyama, Jun Ichi Hata

Research output: Contribution to journalArticlepeer-review

79 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)45-48
Number of pages4
JournalJournal of medical genetics
Issue number1
Publication statusPublished - 1998
Externally publishedYes


  • Frasier syndrome
  • Intronic mutation
  • WT1 gene

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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