Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation in NEUROD1.

Abstract:

BACKGROUND:The aim of the study was to search for mutations in the NEUROD1 and IPF-1 genes in patients with clinical characteristics of maturity-onset diabetes of the young (MODY) but with no mutations in the HNF-4A (MODY1), GCK (MODY2) and TCF1 (MODY3) genes. METHODS:We studied 30 unrelated Czech probands with a clinical diagnosis of MODY (median age at testing, 18 yr; median age at the recognition of hyperglycaemia, 16 yr). The promoter, exons and exon/intron boundaries of the NEUROD1 and IPF-1 genes were examined by polymerase chain reaction-denaturing high performance liquid chromatography and direct sequencing. RESULTS:While no mutations were found in the IPF-1 gene, a novel H241Q substitution of NEUROD1 gene was identified in two unrelated families. In the first proband, the H241Q mutation led to early diagnosed (20 yr) hyperglycaemia followed by development of diabetic microvascular complications by the age of 32 yr. The second proband suffered from slowly progressing hyperglycaemia detected at the age of 30 yr. Affected members of both families were obese. The overall prevalence of the variant among the general population was 4 of 13 568 chromosomes. CONCLUSIONS:We report a novel disease-associated variant in NEUROD1 identified among a set of MODYX families. The variant seems to precipitate type-2-like diabetes in excessively obese individuals.

journal_name

Pediatr Diabetes

journal_title

Pediatric diabetes

authors

Gonsorcíková L,Průhová S,Cinek O,Ek J,Pelikánová T,Jørgensen T,Eiberg H,Pedersen O,Hansen T,Lebl J

doi

10.1111/j.1399-5448.2008.00379.x

subject

Has Abstract

pub_date

2008-08-01 00:00:00

pages

367-72

issue

4 Pt 2

eissn

1399-543X

issn

1399-5448

pii

PDI379

journal_volume

9

pub_type

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