[PDF][PDF] Mutations in hepatocyte nuclear factor 1 are not a common cause of maturity-onset diabetes of the young in the UK

F Beards, T Frayling, M Bulman, Y Horikawa… - DIABETES-NEW …, 1998 - academia.edu
F Beards, T Frayling, M Bulman, Y Horikawa, L Allen, M Appleton, GI Bell, S Ellard
DIABETES-NEW YORK-, 1998academia.edu
Maturity-onset diabetes of the young (MODY) is a monogenic form of type 2 diabetes
characterized by autosomal dominant inheritance, an early age of onset (usually< 25 years
of age), andcell dysfunction (1). MODY is genetically heterogeneous, resulting from
mutations in at least five genes. The most co mmonly identified c ause of MODY in mo st rac
es is a mutation in the hepatocyte nuclear factor (HNF)-1 gene (MODY3)(2–4). Mutations in
the glucokinase (MODY2)(5, 6) and HNF-4 (MODY1) genes (7–9) have been reported in a …
Maturity-onset diabetes of the young (MODY) is a monogenic form of type 2 diabetes characterized by autosomal dominant inheritance, an early age of onset (usually< 25 years of age), andcell dysfunction (1). MODY is genetically heterogeneous, resulting from mutations in at least five genes. The most co mmonly identified c ause of MODY in mo st rac es is a mutation in the hepatocyte nuclear factor (HNF)-1 gene (MODY3)(2–4). Mutations in the glucokinase (MODY2)(5, 6) and HNF-4 (MODY1) genes (7–9) have been reported in a number of pedigrees from many different racial groups. R ecently, mutations in the insulin promoter factor 1 (IPF-1)(10) and the HNF-1 (also known as TCF2) genes (11) have been shown to cosegregate with early-onset diabetes in single MODY pedigrees. The prevalence of mutations in these latter two genes in MODY is uncertain. The HNF-1 gene encodes a homeodomain-containing transcription factor that is a member of a complex transcriptional regulatory network that includes HNF-1 and HNF-4. The HNF-1 and HNF-1 proteins share a high degree of sequence homology (12). HNF-1 functions as a homodimer or a heterodimer with HNF-1 (13, 14) and is a candidate gene for MODY. Strong evidence that mutations in the HNF-1 gene result in MODY came from the description of a nonsense mutation in codon 177 (R177X) in 1 of 57 Japanese pro bands with early-onset type 2 diabetes (11). This mutatio n was present in the proband diagnosed at the age of 10 years, her younger brother, who was diagnosed at the age of 15 years, and their diabetic mother (diagnosed at the age of 40 years). The father was also diabetic (diagnosed at the age of 50 years) but did not carry the mutation. All subjects with the
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