title: A novel mutation of the SLC25A13 gene in a Chinese patient with citrin deficiency detected by target next-generation sequencing.
abstract: Type II citrullinaemia, also known as citrin deficiency, is an autosomal recessive metabolic disorder, which is caused by pathogenic mutations in the SLC25A13 gene on chromosome 7q21.3. One of the clinical manifestations of type II citrullinaemia is neonatal intrahepatic cholestatic hepatitis caused by citrin deficiency (NICCD, OMIM# 605814). In this study, a 5-month-old female Chinese neonate diagnosed with type II citrullinaemia was examined. The diagnosis was based on biochemical and clinical findings, including organic acid profiling using a gas chromatography mass spectrometry (GC/MS), and the patient's parents were unaffected. Approximately 14 kb of the exon sequences of the SLC25A13 and two relative genes (ASS1 and FAH) from the proband and 100 case-unrelated controls were captured by array-based capture method followed by high-throughput next-generation sequencing. Two single-nucleotide mutations were detected in the proband, including the previous reported c.1177+1G>A mutation and a novel c.754 G>A mutation in the SLC25A13 gene. Sanger sequence results showed that the patient was a compound heterozygote for the two mutations. The novel mutation (c.754 G>A), which is predicted to affect the normal structure and function of citrin, is a candidate pathogenic mutation. Target sequence capture combined with high-throughput next-generation sequencing technologies is proven to be an effective method for molecular genetic testing of type II citrullinaemia.
authors.affiliation: School of Bioscience & Bioengineering, South China University of Technology, Guangzhou 510640, China; BGI-Shenzhen, Shenzhen 518083, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Liu
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Wei
authors.forename: Rui
authors.initials: R
authors.lastname: Chen
authors.forename: Hanlin
authors.initials: H
authors.lastname: Zhou
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Li
authors.forename: Yan
authors.initials: Y
authors.lastname: Sun
authors.forename: Shuqi
authors.initials: S
authors.lastname: Xie
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhu
authors.forename: Ning
authors.initials: N
authors.lastname: Qu
authors.forename: Guanghui
authors.initials: G
authors.lastname: Yang
authors.forename: Yuxing
authors.initials: Y
authors.lastname: Chu
authors.forename: Haitao
authors.initials: H
authors.lastname: Wu
authors.forename: Zhangzhang
authors.initials: Z
authors.lastname: Lan
authors.forename: Jinming
authors.initials: J
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Yang
authors.forename: Xin
authors.initials: X
authors.lastname: Yi
mesh_terms: D000595:Amino Acid Sequence; D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002135:Calcium-Binding Proteins / Q000172:deficiency*; D016022:Case-Control Studies; D020159:Citrullinemia / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D006801:Humans; D007223:Infant; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics*; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D027361:Organic Anion Transporters / Q000172:deficiency*
chemical_list: D002135:Calcium-Binding Proteins; D033681:Mitochondrial Membrane Transport Proteins; D027361:Organic Anion Transporters; C119629:SLC25A13 protein, human; C008822:citrin
keywords: A; AA; ALP; ALT; ASS; ASS1; AST; BWA; Burrows Wheeler Aligner; C; CTLN; CTLN1; CTLN2; E; FAH; FTTDCD; G; GC/MS; GGT; Glu; HBV; HCV; HIV; K; Lys; NGS; NICCD; Next generation sequencing; Novel mutation; PCR; PLA; PPA; PSTI; SLC25A13; SNP; T; Target sequence capture; Type II citrullinaemia; adenosine; adult-onset type II citrullinaemia; alanine transaminase; alkaline phosphatase; amino acid(s); argininosuccinate synthetase 1; aspartate aminotransferase; base pair(s); bp; citrullinaemia; cytidine; failure to thrive and dyslipidaemia caused by citrin deficiency; gDNA; gamma glutamyltransferase; gas chromatography mass spectrometry; gene encoding argininosuccinate synthase 1; gene encoding citrin; gene encoding fumarylacetoacetate hydrolase; genomic DNA; glutamic acid; guanosine; hepatitis B virus; hepatitis C virus; human immunodeficiency virus; lysine; neonatal intrahepatic cholestatic hepatitis caused by citrin deficiency; next-generation sequencing; nt; nucleotide(s); pancreatic secretory protease inhibitor; phenylacetic acid; phenylpyruvic acid; polymerase chain reaction; single-nucleotide polymorphism; thymidine; type I citrullinaemia