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

Aims/hypothesis. Five different types of maturity-onset diabetes of the you ng (MODY) have been identified until now but mutation screening suggests th at 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 Ice land 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 as sociated with MODY. Mutations were identified by direct sequencing. Results. Three families were identified. Two of these showed linkage to chr omosome 12 and carried mutations in exon 4 of the HNF-1a gene (290fsdelC an d R272C). However, the third family showed no linkage to the previously des cribed MODY genes but shared a novel mutation in the NeuroD1 gene on chromo some 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.