The IHPK1 gene is disrupted at the 3p21.31 breakpoint of t(3;9) in a family with type 2 diabetes mellitus.
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.
Kamimura
Junichi
J
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.
Wakui
Keiko
K
Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
Kadowaki
Hiroko
H
Department of Clinical Bioinformatics, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
Watanabe
Yukio
Y
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan.
Miyake
Kazuaki
K
Division of Diabetes, Digestive and Kidney Disease, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Harada
Naoki
N
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.
Sakamoto
Michiyo
M
Division of Pediatrics, Yamagata City Hospital Saiseikan, Yamagata, Japan.
Kinoshita
Akira
A
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
Yoshiura
Koh-Ichiro
KI
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
Ohta
Tohru
T
CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|Division of Functional Genomics, Research Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.
Kishino
Tatsuya
T
CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|Division of Functional Genomics, Research Center for Frontier Life Sciences, Nagasaki University, Nagasaki, Japan.
Ishikawa
Mutsuo
M
Department of Obstetrics and Gynecology, Asahikawa Medical College, Asahikawa, Japan.
Kasuga
Masato
M
Division of Diabetes, Digestive and Kidney Disease, Department of Clinical Molecular Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
Fukushima
Yoshimitsu
Y
CREST, Japan Science and Technology Agency, Kawaguchi, Japan.|Department of Medical Genetics, Shinshu University School of Medicine, Matsumoto, Japan.
Niikawa
Norio
N
Department of Human Genetics, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.|CREST, Japan Science and Technology Agency, Kawaguchi, Japan.
Matsumoto
Naomichi
N
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.
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
D017856:Phosphotransferases (Phosphate Group Acceptor); C115134:IP6K1 protein, human