Aims/hypothesis. Five different types of maturity-on-set 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-1α 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.
|Number of pages||6|
|Publication status||Published - 2001|
Bibliographical noteFunding Information:
Acknowledgements. We would like to thank the University of Iceland Research Fund, The Icelandic Research Council (RANNIS) and Iceland Genomics Corporation for financial support. We would also like to thank Thorunn Rafnar, PhD, for helpful comments in preparing this study and G. J. Gun-narsson for technical assistance.