title: The IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus.
abstract: 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.
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
authors.forename: Junichi
authors.initials: J
authors.lastname: Kamimura
authors.affiliation: Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Keiko
authors.initials: K
authors.lastname: Wakui
authors.affiliation: Department of Clinical Bioinformatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Kadowaki
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan.
authors.forename: Yukio
authors.initials: Y
authors.lastname: Watanabe
authors.affiliation: Division of Diabetes, Digestive and Kidney Disease, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Miyake
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|Kyushu Medical Science Nagasaki Laboratory, Nagasaki, Japan.
authors.forename: Naoki
authors.initials: N
authors.lastname: Harada
authors.affiliation: Division of Pediatrics, Yamagata City Hospital Saiseikan, Yamagata, Japan.
authors.forename: Michiyo
authors.initials: M
authors.lastname: Sakamoto
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kinoshita
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
authors.forename: Koh-Ichiro
authors.initials: KI
authors.lastname: Yoshiura
authors.affiliation: CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|Division of Functional Genomics, Research Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Ohta
authors.affiliation: CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|Division of Functional Genomics, Research Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kishino
authors.affiliation: Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan.
authors.forename: Mutsuo
authors.initials: M
authors.lastname: Ishikawa
authors.affiliation: Division of Diabetes, Digestive and Kidney Disease, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Kasuga
authors.affiliation: CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
authors.forename: Yoshimitsu
authors.initials: Y
authors.lastname: Fukushima
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
authors.forename: Norio
authors.initials: N
authors.lastname: Niikawa
authors.affiliation: Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan. naomat@yokohama-cu.ac.jp.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan. naomat@yokohama-cu.ac.jp.|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.
authors.forename: Naomichi
authors.initials: N
authors.lastname: Matsumoto
mesh_terms: D000293:Adolescent; D022202:Chromosomes, Artificial, Bacterial; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D003001:Cloning, Molecular; D003360:Cosmids / Q000378:metabolism; D004252:DNA Mutational Analysis; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005091:Exons; D005192:Family Health; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008957:Models, Genetic; D009154:Mutation; D017856:Phosphotransferases (Phosphate Group Acceptor) / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012984:Software; D014178:Translocation, Genetic
chemical_list: D017856:Phosphotransferases (Phosphate Group Acceptor); C115134:IP6K1 protein, human