Autosomal inheritance of diabetes in two families characterized by obesity and a novel H241Q mutation inNEUROD1
- 29 July 2008
- journal article
- Published by Hindawi Limited in Pediatric Diabetes
- Vol. 9 (4pt2), 367-372
- https://doi.org/10.1111/j.1399-5448.2008.00379.x
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.Keywords
This publication has 17 references indexed in Scilit:
- A novel mutation, Ser159Pro in the NeuroD1/BETA2 gene contributes to the development of diabetes in a Chinese potential MODY familyMolecular and Cellular Biochemistry, 2007
- Diagnostic screening of NEUROD1 (MODY6) in subjects with MODY or gestational diabetes mellitusDiabetic Medicine, 2005
- MODY in Iceland is associated with mutations in HNF -1? and a novel mutation in NeuroD1Diabetologia, 2001
- Molecular Mechanisms and Clinical Pathophysiology of Maturity-Onset Diabetes of the YoungNew England Journal of Medicine, 2001
- Mutations in NEUROD1 are associated with the development of type 2 diabetes mellitusNature Genetics, 1999
- Missense mutations in the insulin promoter factor-1 gene predispose to type 2 diabetesJCI Insight, 1999
- β-Cell Transcription Factors and Diabetes: Mutations in the Coding Region of the BETA2/NeuroD1 (NEUROD1) and Nkx2.2 (NKX2B) Genes Are Not Associated With Maturity-Onset Diabetes of the Young in JapaneseDiabetes, 1998
- Organization and Partial Sequence of the Hepatocyte Nuclear Factor-4α/MODY1 Gene and Identification of a Missense Mutation, R127W, in a Japanese Family With MODYDiabetes, 1997
- Pancreatic agenesis attributable to a single nucleotide deletion in the human IPF1 gene coding sequenceNature Genetics, 1997
- Tissue-specific regulation of the insulin gene by a novel basic helix-loop-helix transcription factor.Genes & Development, 1995