Details

Autor(en) / Beteiligte

• HORIKAWA, Yohko
• HORIKAWA, Yukio
• COX, Nancy J
• IWASAKI, Naoko
• OGATA, Makiko
• IWAMOTO, Yasuhiko
• SCHWITZGEBEL, Valerie
• GERMAN, Michael S
• BELL, Graeme I

Titel

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

Ist Teil von

• Diabetes (New York, N.Y.), 2000-11, Vol.49 (11), p.1955-1957

Ort / Verlag

Alexandria, VA: American Diabetes Association

Erscheinungsjahr

2000

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. Y Horikawa , Y Horikawa , N J Cox , N Iwasaki , M Ogata , Y Iwamoto , V Schwitzgebel , M S German and G I Bell Department of Biochemistry and Molecular Biology, The University of Chicago, Illinois, USA. 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.