title: Screening for five prevalent mutations of SLC25A13 gene in Guangdong, China: a molecular epidemiologic survey of citrin deficiency.
abstract: Citrin is the liver-type aspartate/glutamate carrier isoform 2 (AGC2) encoded by SLC25A13 gene, playing important roles in the urea cycle and the malate-aspartate shuttle. Citrin deficiency (CD) has proven a disease entity with high prevalence in south China, including Guangdong with the largest population, but CD epidemiology in this province has not been well characterized. This study aims to screen for five prevalent SLC25A13 mutations, c.851_854del (p.R284fs286X), c.1638_1660dup (p.A554fs570X), c.615+5G>A (p.A206fs212X), IVS16ins3kb (p.A584fs585X) and c.1399C>T (p.R467X), to calculate the mutation carrier rate in Guangdong. A total of 2,428 used blood samples for health examination were collected as the research subjects, including 1,558 from 5 cities in the Pearl River Delta area and the remaining 870 from 4 peripheral cities, and the 5 mutations screened using High Resolution Melting Assay and HybProbe assay. A total of 52 carriers were detected, including 2 carriers of a novel c.1420G>A (p.V474M) mutation that impairs citrin function, as judged by the functional analysis in the yeast system. The carrier rate was higher in Pearl River Delta area than that in the peripheral cities (26/1,558 vs. 26/870, with χ(2) = 4.639 and P < 0.05). The carrier rate was around 1/47 (52/2,428), theoretically with the CD morbidity of 1/8,800 and the number of CD patients over 11,800 in Guangdong population. This study has provided primary epidemiologic data for the evaluation of CD effect in Guangdong province. Moreover, the newly identified c.1420G>A mutation that impairs AGC2 function has enriched the mutation spectrum of human SLC25A13 gene.
authors.affiliation: Department of Pediatrics, The First Afﬁliated Hospital, Jinan University.
authors.forename: Zhan-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: Yang
authors.forename: Feng-Ping
authors.initials: FP
authors.lastname: Chen
authors.forename: Atsuo
authors.initials: A
authors.lastname: Kikuchi
authors.forename: Zhen-Huan
authors.initials: ZH
authors.lastname: Liu
authors.forename: Li-Zhen
authors.initials: LZ
authors.lastname: Kuang
authors.forename: Wei-Ming
authors.initials: WM
authors.lastname: Li
authors.forename: Yuan-Zong
authors.initials: YZ
authors.lastname: Song
authors.forename: Shigeo
authors.initials: S
authors.lastname: Kure
authors.forename: Takeyori
authors.initials: T
authors.lastname: Saheki
mesh_terms: D001483:Base Sequence; D002681:China / Q000453:epidemiology; D020159:Citrullinemia / Q000453:epidemiology* / Q000235:genetics*; D005820:Genetic Testing; D005843:Geography; D006579:Heterozygote; D006801:Humans; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D017720:Molecular Epidemiology; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D009691:Nucleic Acid Denaturation
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; C119629:SLC25A13 protein, human