title: Screening of SLC25A13 mutation in the Thai population.
abstract: OBJECTIVE
  To determine the prevalence of SLC25A13 mutations in the Thai population.
  
  
  METHODS
  A total of 1537 subjects representing the Thai population were screened for a novel pathologic allele p.Met1? (c.2T > C) and six previously known common SLC25A13 mutations: [I] (c.851_854delGTAT), [II] (g.IVS11 + 1G > A), [III] (c.1638_1660dup), [IV] (p.S225X), [V] (IVS13 + 1G > A), and [XIX] (g.IVS16ins3kb) using a newly developed TaqMan and established HybProbe assay, respectively. Sanger sequencing was employed for specimens showing an aberrant peak to confirm the targeted mutation as well as the unknown aberrant peaks detected. Frequencies of the mutations identified were compared in each region. Carrier frequency and disease prevalence of citrin deficiency caused by SCL25A13 mutations were estimated.
  
  
  RESULTS
  p.Met1? was identified in the heterozygous state in 85 individuals, giving a carrier frequency of 1/18, which suggests possible selective advantage of this variant. The question of p.Met1? homozygote lethality remains unanswered which may serve as an explanation as to why this homozygote has yet to be identified in patients/controls even with high allele frequency. The p.Met1? mutation has rarely been studied in populations other than Thai and Chinese; therefore, may have been overlooked. Development of the TaqMan assay in the present study would allow a simple, rapid, and cost-effective method for mass screening. Heterozygous mutations: [XIX] and [I] were identified in 17 individuals, giving a carrier rate of 1/90 and a calculated homozygote rate of 1/33000. Two novel variants, g.IVS11 + 17C > G and c.1311C > T, of unknown clinical significance were identified at low frequency.
  
  
  CONCLUSIONS
  This study highlighted the current underestimation of citrin deficiency and suggests the possible selective advantage of the p.Met1? allele.
authors.affiliation: Parith Wongkittichote, Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok 10400, Thailand.
authors.forename: Parith
authors.initials: P
authors.lastname: Wongkittichote
authors.forename: Chonlaphat
authors.initials: C
authors.lastname: Sukasem
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Wichai
authors.initials: W
authors.lastname: Aekplakorn
authors.forename: Laran T
authors.initials: LT
authors.lastname: Jensen
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Duangrurdee
authors.initials: D
authors.lastname: Wattanasirichaigoon
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People / Q000235:genetics*; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D020159:Citrullinemia / Q000208:ethnology / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D027361:Organic Anion Transporters / Q000172:deficiency*; D015995:Prevalence; D013785:Thailand / Q000453:epidemiology
chemical_list: D002135:Calcium-Binding Proteins; D033681:Mitochondrial Membrane Transport Proteins; D027361:Organic Anion Transporters; C119629:SLC25A13 protein, human; C008822:citrin
keywords: Aspartate-glutamate carrier; Citrin deficiency; Isoform 2; Neonatal intrahepatic cholestasis caused by citrin deficiency; SLC25A13; Type II citrullinemia