PMID- 15221640 OWN - NLM STAT- MEDLINE DCOM- 20040824 LR - 20200209 IS - 1434-5161 (Print) IS - 1434-5161 (Linking) VI - 49 IP - 7 DP - 2004 TI - The IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus. PG - 360-365 LID - 10.1007/s10038-004-0158-z [doi] AB - Type 2 diabetes mellitus (T2DM) is a group of multifactorial disorders due to either defective insulin secretion or action. Despite the fact that numerous genetic researches of T2DM have been pursued, the pathogenic mechanisms remain obscure. We encountered a T2DM family associated with a balanced reciprocal translocation, t(3;9)(p21.31;q33.1). To isolate a candidate gene susceptible to T2DM, we constructed physical maps covering both the 3p and 9q breakpoints of the translocation in the family. Consequently, the inositol hexaphosphate kinase 1 gene ( IHPK1) (OMIM *606991) was found to be disrupted at the 3p21.31 breakpoint. We then carried out sequence analysis for all coding regions of IHPK1 in 405 unrelated T2DM patients in order to validate whether aberrations of the gene are common in T2DM patients, but we failed to detect any pathogenic changes. The disruption of IHPK1 or another predisposing gene affected by position effect of the translocation may explain the T2DM phenotype at least in this family. Alternatively, the IHPK1 disruption in the family is a chance association. FAU - Kamimura, Junichi AU - Kamimura J AD - Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. AD - Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan. AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. FAU - Wakui, Keiko AU - Wakui K AD - Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. FAU - Kadowaki, Hiroko AU - Kadowaki H AD - Department of Clinical Bioinformatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan. FAU - Watanabe, Yukio AU - Watanabe Y AD - Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. AD - Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan. FAU - Miyake, Kazuaki AU - Miyake K AD - Division of Diabetes, Digestive and Kidney Disease, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Harada, Naoki AU - Harada N AD - Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. AD - Kyushu Medical Science Nagasaki Laboratory, Nagasaki, Japan. FAU - Sakamoto, Michiyo AU - Sakamoto M AD - Division of Pediatrics, Yamagata City Hospital Saiseikan, Yamagata, Japan. FAU - Kinoshita, Akira AU - Kinoshita A AD - Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. FAU - Yoshiura, Koh-Ichiro AU - Yoshiura KI AD - Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. FAU - Ohta, Tohru AU - Ohta T AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. AD - Division of Functional Genomics, Research Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan. FAU - Kishino, Tatsuya AU - Kishino T AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. AD - Division of Functional Genomics, Research Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan. FAU - Ishikawa, Mutsuo AU - Ishikawa M AD - Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan. FAU - Kasuga, Masato AU - Kasuga M AD - Division of Diabetes, Digestive and Kidney Disease, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan. FAU - Fukushima, Yoshimitsu AU - Fukushima Y AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. AD - Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan. FAU - Niikawa, Norio AU - Niikawa N AD - Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. FAU - Matsumoto, Naomichi AU - Matsumoto N AD - Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. naomat@yokohama-cu.ac.jp. AD - CREST, Japan Science and Technology Agency, Kawaguchi, Japan. naomat@yokohama-cu.ac.jp. AD - Department of Human Genetics, Yokohama City University Graduate School of Medicine, 3-9 Fukuura, Kanazawa-ku, Yokohama 236-0004, Japan. naomat@yokohama-cu.ac.jp. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20040618 PL - England TA - J Hum Genet JT - Journal of human genetics JID - 9808008 RN - EC 2.7.4.- (Phosphotransferases (Phosphate Group Acceptor)) RN - EC 2.7.4.21 (IP6K1 protein, human) SB - IM MH - Adolescent MH - Chromosomes, Artificial, Bacterial MH - *Chromosomes, Human, Pair 3 MH - *Chromosomes, Human, Pair 9 MH - Cloning, Molecular MH - Cosmids/metabolism MH - DNA Mutational Analysis MH - Diabetes Mellitus, Type 2/*genetics MH - Exons MH - Family Health MH - Female MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Models, Genetic MH - Mutation MH - Phosphotransferases (Phosphate Group Acceptor)/*genetics MH - Sequence Analysis, DNA MH - Software MH - *Translocation, Genetic EDAT- 2004/06/29 05:00 MHDA- 2004/08/25 05:00 CRDT- 2004/06/29 05:00 PHST- 2004/03/10 00:00 [received] PHST- 2004/03/31 00:00 [accepted] PHST- 2004/06/29 05:00 [pubmed] PHST- 2004/08/25 05:00 [medline] PHST- 2004/06/29 05:00 [entrez] AID - 10.1007/s10038-004-0158-z [pii] AID - 10.1007/s10038-004-0158-z [doi] PST - ppublish SO - J Hum Genet. 2004;49(7):360-365. doi: 10.1007/s10038-004-0158-z. Epub 2004 Jun 18.