title: beta-cell transcription factors and diabetes: no evidence for diabetes-associated mutations in the gene encoding the basic helix-loop-helix transcription factor neurogenic differentiation 4 (NEUROD4) in Japanese patients with MODY.
abstract: The basic helix-loop-helix (bHLH) family of transcription factors plays an important role in the normal development and function of the endocrine pancreas. Heterozygous mutations in the gene encoding one member of this family, NeuroD1/BETA2, are associated with a monogenic form of diabetes that resembles maturity-onset diabetes of the young (MODY) in many respects. This result prompted us to screen the genes encoding related bHLH transcription factors that are also expressed in pancreatic islets for diabetes-associated mutations. We have screened 57 unrelated Japanese subjects with a clinical diagnosis of MODY for mutations in the NeuroD4/Math-3/ATH-3 gene (NEUROD4). This analysis revealed seven frequent polymorphisms that were not associated with MODY, including five in the 5'-untranslated region (UTR) (-477G/A, -436delA, -324delT, -107insTTTT, and -104T/C [cDNA sequences]) and two in the 3'-UTR (1027C/T and 1076C/A). A missense mutation, K68T (203A/C), was found in a heterozygous state in one MODY subject and two nondiabetic subjects. The results of our study suggest that genetic variation in NEUROD4 is not a common cause of MODY in Japanese.
authors.affiliation: Department of Biochemistry and Molecular Biology, The University of Chicago, Illinois, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Horikawa
authors.forename: Y
authors.initials: Y
authors.lastname: Horikawa
authors.forename: N J
authors.initials: NJ
authors.lastname: Cox
authors.forename: N
authors.initials: N
authors.lastname: Iwasaki
authors.forename: M
authors.initials: M
authors.lastname: Ogata
authors.forename: Y
authors.initials: Y
authors.lastname: Iwamoto
authors.forename: V
authors.initials: V
authors.lastname: Schwitzgebel
authors.forename: M S
authors.initials: MS
authors.lastname: German
authors.forename: G I
authors.initials: GI
authors.lastname: Bell
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D018257:Helix-Loop-Helix Motifs / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism*; D007564:Japan; D009154:Mutation; D020125:Mutation, Missense; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009479:Neuropeptides; D011110:Polymorphism, Genetic; D014157:Transcription Factors; D020506:Untranslated Regions
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D014157:Transcription Factors; D020506:Untranslated Regions; C498274:DPF1 protein, human; C490925:NEUROD2 protein, human; C490924:Neurod2 protein, rat