MODY in Iceland is associated with mutations in HNF-1alpha and a novel mutation in NeuroD1

Diabetologia. 2001 Nov;44(11):2098-103. doi: 10.1007/s001250100016.


Aims/hypothesis: Five different types of maturity-onset diabetes of the young (MODY) have been identified until now but mutation screening suggests that more MODY genes exist. Mutations in genes encoding transcription factors essential for normal development and function of pancreatic beta cells has recently become important in studying the genetics of Type II (non-insulin-dependent) diabetes mellitus. Patients with MODY and their families in Iceland were screened for mutations in the transcription factor genes.

Methods: Clinical and biochemical information on individuals with MODY was collected and their family trees constructed. Linkage analysis was carried out on chromosomal regions known to harbour genes previously shown to be associated with MODY. Mutations were identified by direct sequencing.

Results: Three families were identified. Two of these showed linkage to chromosome 12 and carried mutations in exon 4 of the HNF-1alpha gene (290fsdelC and R272C). However, the third family showed no linkage to the previously described MODY genes but shared a novel mutation in the NeuroD1 gene on chromosome 2q32. This mutation, a glutamate to lysine substitution at codon 110, resides in the basic domain of the protein.

Conclusion/interpretation: Mutations in MODY subjects have been identified in the Icelandic population. In addition this study identified the NeuroD1 gene as the gene responsible for the sixth type of MODY.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Age of Onset
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins / genetics*
  • Diabetes Mellitus, Type 1 / genetics
  • Diabetes Mellitus, Type 2 / genetics*
  • Diabetes, Gestational / genetics
  • Female
  • Genetic Markers
  • Glucose Tolerance Test
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-alpha
  • Hepatocyte Nuclear Factor 1-beta
  • Humans
  • Mutation*
  • Nuclear Proteins*
  • Pedigree
  • Pregnancy
  • Reference Values
  • Trans-Activators / genetics*
  • Transcription Factors / genetics*


  • Basic Helix-Loop-Helix Transcription Factors
  • DNA-Binding Proteins
  • Genetic Markers
  • HNF1A protein, human
  • HNF1B protein, human
  • Hepatocyte Nuclear Factor 1-alpha
  • NEUROD1 protein, human
  • Nuclear Proteins
  • Trans-Activators
  • Transcription Factors
  • Hepatocyte Nuclear Factor 1
  • Hepatocyte Nuclear Factor 1-beta