title: Molecular diagnosis of pediatric patients with citrin deficiency in China: SLC25A13 mutation spectrum and the geographic distribution.
abstract: Citrin deficiency (CD) is a Mendelian disease due to biallelic mutations of SLC25A13 gene. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major pediatric CD phenotype, and its definite diagnosis relies on SLC25A13 genetic analysis. China is a vast country with a huge population, but the SLC25A13 genotypic features of CD patients in our country remains far from being well clarified. Via sophisticated molecular analysis, this study diagnosed 154 new CD patients in mainland China and identified 9 novel deleterious SLC25A13 mutations, i.e. c.103A > G, [c.329 - 154_c.468 + 2352del2646; c.468 + 2392_c.468 + 2393ins23], c.493C > T, c.755 - 1G > C, c.845_c.848 + 1delG, c.933_c.933 + 1insGCAG, c.1381G > T, c.1452 + 1G > A and c.1706_1707delTA. Among the 274 CD patients diagnosed by our group thus far, 41 SLC25A13 mutations/variations were detected. The 7 mutations c.775C > T, c.851_854del4, c.1078C > T, IVS11 + 1G > A, c.1364G > T, c.1399C > T and IVS16ins3kb demonstrated significantly different geographic distribution. Among the total 53 identified genotypes, only c.851_854del4/c.851_854del4 and c.851_854del4/c.1399C > T presented different geographic distribution. The northern population had a higher level of SLC25A13 allelic heterogeneity than those in the south. These findings enriched the SLC25A13 mutation spectrum and brought new insights into the geographic distribution of the variations and genotypes, providing reliable evidences for NICCD definite diagnosis and for the determination of relevant molecular targets in different Chinese areas.
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Wei-Xia
authors.initials: WX
authors.lastname: Lin
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Han-Shi
authors.initials: HS
authors.lastname: Zeng
authors.affiliation: Clinical Medicine Research Institute, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Zhan-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Department of Laboratory Science, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Man
authors.initials: M
authors.lastname: Mao
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Qi-Qi
authors.initials: QQ
authors.lastname: Zheng
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Shu-Tao
authors.initials: ST
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Cheng
authors.affiliation: Department of Laboratory Science, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Feng-Ping
authors.initials: FP
authors.lastname: Chen
authors.affiliation: Department of Laboratory Science, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Wang-Rong
authors.initials: WR
authors.lastname: Wen
authors.affiliation: Department of Pediatrics, the First Affiliated Hospital, Jinan University, Guangzhou, 510630, China.
authors.forename: Yuan-Zong
authors.initials: YZ
authors.lastname: Song
mesh_terms: D044466:Asian People / Q000235:genetics*; D002681:China / Q000453:epidemiology; D020159:Citrullinemia / Q000453:epidemiology* / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D017720:Molecular Epidemiology / Q000379:methods; D009154:Mutation; D057089:Pathology, Molecular / Q000379:methods
chemical_list: D033681:Mitochondrial Membrane Transport Proteins; C119629:SLC25A13 protein, human