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Mutations in the hepatocyte nuclear factor-1alpha (HNF1alpha) gene have recently been shown to cause maturity-onset diabetes of the young (MODY). We have examined 15 U.K. MODY families for mutations in the coding region of the HNF-1alpha gene. Eight different mutations, three frameshift (P291fsinsC, P379fsdelCT, and A443fsdelCA) and five missense mutations (P129T, R131W, R159W, P519L, and T620I), were identified in eleven families (73%). The previously reported mutation P291fsinsC was found in four pedigrees. A screen of a further 32 probands with early onset (<40 years of age) NIDDM showed the mutation in two additional families. This common mutation was present on at least three different haplotypes, suggesting that its high frequency is due to recurrent mutation rather than a founder effect. We have demonstrated that mutations in the HNF-1alpha gene are a common cause of MODY in U.K. families and result in early onset NIDDM with a progressive clinical course. Mutation-based genetic counseling can now be considered for the majority of patients with MODY.

Original publication

DOI

10.2337/diab.46.4.720

Type

Journal article

Journal

Diabetes

Publication Date

04/1997

Volume

46

Pages

720 - 725

Addresses

Institute of Clinical Science, University of Exeter, Devon, U.K.

Keywords

Humans, Diabetes Mellitus, Type 2, DNA-Binding Proteins, Nuclear Proteins, Transcription Factors, Pedigree, Family, Haplotypes, Mutation, Polymorphism, Genetic, Adolescent, Adult, Aged, Middle Aged, Child, Hepatocyte Nuclear Factor 1, Hepatocyte Nuclear Factor 1-alpha, Hepatocyte Nuclear Factor 1-beta, United Kingdom