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Screening of SLC25A13 mutation in the Thai population
Parith Wongkittichote, Chonlaphat Sukasem, Atsuo Kikuchi, Wichai Aekplakorn, Laran T Jensen, Shigeo Kure, Duangrurdee Wattanasirichaigoon
Parith Wongkittichote, Graduate Program in Molecular Medicine, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Chonlaphat Sukasem, Division of Pharmacogenomics and Personalized Medicine, Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Atsuo Kikuchi, Shigeo Kure, Department of Pediatrics, Tohoku University Graduate School of Medicine, Sendai 980-8577, Japan
Wichai Aekplakorn, Department of Community Medicine, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
Laran T Jensen, Department of Biochemistry, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
Duangrurdee Wattanasirichaigoon, Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok, 10400 Thailand
Author contributions: Wongkittichote P and Sukasem C designed the study, performed experiments, analyzed and interpreted data, drafted and revised the article; Kikuchi A designed the study, performed experiments, revised the article; Aekplakorn W designed the study, analyzed and interpreted data, revised the article; Jensen LT was involved in conception of the study, revised the article; Kure S was involved in the conception and design of the study, analyzed, interpreted data, and revised the article; and Wattanasirichaigoon D was involved in the conception and design of the study, analyzed, interpreted data, drafted and revised the article
Supported by A joint grant from Mahidol University Faculty of Science and Ramathibodi Hospital Faculty of Medicine (Jensen LT and Wattanasirichaigoon D); Mahidol University (Wattanasirichaigoon D: 49/2556); the Pharmacogenomics Project, the collaborative project from the Thailand Center of Excellence for Life Science and Mahidol University to Sukasem C; and the Medical Scholars Program of Mahidol University (Wongkittichote P); a recipient (Wattanasirichaigoon D) of Research Career Development Award, Faculty of Medicine Ramathibodi Hospital
Correspondence to: Duangrurdee Wattanasirichaigoon, MD, Professor of Pediatrics, Division of Medical Genetics, Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand.
duangrurdee.wat@mahidol.ac.th
Telephone: +66-2-2012782 Fax: +66-2-2012783
Received: July 9, 2013
Revised: August 29, 2013
Accepted: September 16, 2013
Published online: November 21, 2013
Processing time: 161 Days and 15.5 Hours
AIM: 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.
CONCLUSION: This study highlighted the current underestimation of citrin deficiency and suggests the possible selective advantage of the p.Met1? allele.
Core tip: Citrin deficiency is underestimated in various populations and the high prevalence of some SLC25A13 variants possibly contribute to uncharacterized predisposition/protection of certain disorders.
