Mutations in the coding region of the neurogenin 3 gene (NEUROG3) are not a common cause of maturity-onset diabetes of the young in Japanese subjects

Mutations in transcription factors that play a role in the development of t he endocrine pancreas, such as insulin promoter factor-1 and NeuroD1/BETA2, have been associated with diabetes. Cell type-specific members of the basi c helix-loop-helix (bHLH) family of transcription factors play essential ro les in the development and maintenance of many differentiated cell types, i ncluding pancreatic beta -cells, Neurogenin 3 is a bHLH transcription facto r that is expressed in the developing central nervous system and the embryo nic pancreas. Mice lacking this transcription factor fail to develop any is let endocrine cells and die postnatally from diabetes. Because neurogenin 3 is required for the development of p-cells and other pancreatic islet cell types, we considered it a candidate diabetes gene. We screened the coding region of the human neurogenin 3 gene (NEUROG3) for mutations in a group of unrelated Japanese subjects with maturity-onset diabetes of the young (MOD Y), We found three sequence variants: a deletion of 2-bp in the 5'-untransl ated region (NEUROG3-g.-4445delCA), a G-to-A substitution in codon 167 (g.4 99G/ A), resulting in a, Gly-to-Arg replacement (G/R167), and a T-to-C subs titution in codon 199 (g.596T/C), resulting in a Phe/Ser polymorphism F/S19 9. These polymorphisms were not associated with MODY, thereby suggesting th at mutations in NEUROG3 are not a common cause of MODY in Japanese patients .