Frequency and distribution in East Asia of 12 mutations identified in the SLC25A13 gene of Japanese patients with citrin deficiency.
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.
Lu
Yao Bang
YB
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Kobayashi
Keiko
K
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.
Ushikai
Miharu
M
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Tabata
Ayako
A
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Iijima
Mikio
M
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Li
Meng Xian
MX
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Lei
Lei
L
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
Kawabe
Kotaro
K
Division of Gene Research, Research Centre for Life Science Resources, Kagoshima University, Kagoshima, Japan.
Taura
Satoru
S
Division of Gene Research, Research Centre for Life Science Resources, Kagoshima University, Kagoshima, Japan.
Yang
Yanling
Y
Department of Pediatrics, The First Hospital of Peking University, Beijing, China.
Liu
Tze-Tze
TT
Genome Research Center, National Yang-Ming University, Taipei, Taiwan, ROC.
Chiang
Szu-Hui
SH
Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Hsiao
Kwang-Jen
KJ
Taipei Veterans General Hospital, Taipei, Taiwan, ROC.
Lau
Yu-Lung
YL
Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
Tsui
Lap-Chee
LC
Vice Chancellor's Office, The University of Hong Kong, Hong Kong SAR, People's Republic of China.
Lee
Dong Hwan
DH
Department of Pediatrics, Soonchunhyang University Hospital, Seoul, Korea.
Saheki
Takeyori
T
Department of Molecular Metabolism and Biochemical Genetics, Kagoshima University Graduate School of Medical and Dental Sciences, 8-35-1 Sakuragaoka, Kagoshima 890-8544, Japan.
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
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