title: Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency.
abstract: Deficiency of citrin, a liver-type mitochondrial aspartate-glutamate carrier (AGC), encoded by the SLC25A13 gene on chromosome 7q21.3, causes autosomal recessive disorders: adult-onset type II citrullinemia (CTLN2) and neonatal hepatitis associated with intrahepatic cholestasis (NICCD). So far, we have described 12 SLC25A13 mutations: 11 were from Japan and one from Israel. Three mutations found in Chinese and Vietnamese patients were the same as those in Japanese patients. In the present study, we identified a novel mutation IVS6+1G>C in a Japanese CTLN2 patient and widely screened 12 SLC25A13 mutations found in Japanese patients in control individuals from East Asia to confirm our preliminary results that the carrier frequency was high in Asian populations. Mutations 851-854del and 1638-1660dup were found in all Asian countries tested, and 851-854del associated with 290-haplotype in microsatellite marker D7S1812 was especially frequent. Other mutations frequently detected were IVS11+1G>A in Japanese and Korean, S225X in Japanese, and IVS6+5G>A in Chinese populations. We found a remarkable difference in carrier rates in China (including Taiwan) between north (1/940) and south (1/48) of the Yangtze River. We detected many carriers in Chinese (64/4169 = 1/65), Japanese (20/1372 = 1/69) and Korean (22/2455 = 1/112) populations, suggesting that over 80,000 East Asians are homozygotes with two mutated SLC25A13 alleles.
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Yao Bang
authors.initials: YB
authors.lastname: Lu
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan. dodoko12@m.kufm.kagoshima-u.ac.jp.
authors.forename: Keiko
authors.initials: K
authors.lastname: Kobayashi
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Miharu
authors.initials: M
authors.lastname: Ushikai
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Tabata
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Mikio
authors.initials: M
authors.lastname: Iijima
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Meng Xian
authors.initials: MX
authors.lastname: Li
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Lei
authors.initials: L
authors.lastname: Lei
authors.affiliation: Division of Gene Research, Research Centre for Life Science Resources, Kagoshima University, Kagoshima, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Kawabe
authors.affiliation: Division of Gene Research, Research Centre for Life Science Resources, Kagoshima University, Kagoshima, Japan.
authors.forename: Satoru
authors.initials: S
authors.lastname: Taura
authors.affiliation: Department of Pediatrics, The First Hospital of Peking University, Beijing, China.
authors.forename: Yanling
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Genome Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.
authors.forename: Tze-Tze
authors.initials: TT
authors.lastname: Liu
authors.affiliation: Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Szu-Hui
authors.initials: SH
authors.lastname: Chiang
authors.affiliation: Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
authors.forename: Kwang-Jen
authors.initials: KJ
authors.lastname: Hsiao
authors.affiliation: Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.affiliation: Vice Chancellor's Office, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
authors.forename: Lap-Chee
authors.initials: LC
authors.lastname: Tsui
authors.affiliation: Department of Pediatrics, Soonchunhyang University Hospital, Seoul, Korea.
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Lee
authors.affiliation: Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
authors.forename: Takeyori
authors.initials: T
authors.lastname: Saheki
mesh_terms: D002135:Calcium-Binding Proteins / Q000172:deficiency*; D020159:Citrullinemia / Q000453:epidemiology* / Q000235:genetics*; D017931:DNA Primers; D005202:Asia, Eastern / Q000453:epidemiology; D040461:Gene Components; D006580:Genetic Carrier Screening; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics*; D018895:Microsatellite Repeats / Q000235:genetics; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D027361:Organic Anion Transporters / Q000172:deficiency*; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D002135:Calcium-Binding Proteins; D017931:DNA Primers; D026901:Membrane Transport Proteins; D033681:Mitochondrial Membrane Transport Proteins; D024101:Mitochondrial Proteins; D027361:Organic Anion Transporters; C119629:SLC25A13 protein, human; C008822:citrin