A novel mutation of the SLC25A13 gene in a Chinese patient with citrin deficiency detected by target next-generation sequencing

• Published in: Gene Vol. 533; no. 2; pp. 547 - 553
• Main Authors: Liu, Gang, Wei, Xiaoming, Chen, Rui, Zhou, Hanlin, Li, Xiaoyan, Sun, Yan, Xie, Shuqi, Zhu, Qian, Qu, Ning, Yang, Guanghui, Chu, Yuxing, Wu, Haitao, Lan, Zhangzhang, Wang, Jinming, Yang, Yi, Yi, Xin
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 10.01.2014
• Subjects: Amino Acid Sequence; Asian Continental Ancestry Group - genetics; Base Sequence; Calcium-Binding Proteins - deficiency; Case-Control Studies; Citrullinemia - genetics; DNA Mutational Analysis - methods; Female; High-Throughput Nucleotide Sequencing - methods; Humans; Infant; Mitochondrial Membrane Transport Proteins - genetics; Molecular Sequence Data; Mutation, Missense; Next generation sequencing; Novel mutation; Organic Anion Transporters - deficiency; SLC25A13; Target sequence capture; Type II citrullinaemia; PPA; A; C; PLA; ALP; E; nt; G; Target sequence capture; CTLN2; ALT; CTLN1; K; BWA; bp; Novel mutation; Glu; SNP; T; HBV; PSTI; gDNA; AA; ASS; AST; NICCD; FTTDCD; Lys; CTLN; FAH; Next generation sequencing; ASS1; Type II citrullinaemia; HIV; GGT; HCV; NGS; GC/MS; PCR; SLC25A13; glutamic acid; gamma glutamyltransferase; hepatitis B virus; type I citrullinaemia; thymidine; alkaline phosphatase; genomic DNA; cytidine; phenylacetic acid; adenosine; lysine; human immunodeficiency virus; failure to thrive and dyslipidaemia caused by citrin deficiency; gene encoding argininosuccinate synthase 1; neonatal intrahepatic cholestatic hepatitis caused by citrin deficiency; nucleotide(s); alanine transaminase; hepatitis C virus; citrullinaemia; single-nucleotide polymorphism; base pair(s); polymerase chain reaction; adult-onset type II citrullinaemia; Burrows Wheeler Aligner; phenylpyruvic acid; argininosuccinate synthetase 1; next-generation sequencing; pancreatic secretory protease inhibitor; amino acid(s); gene encoding citrin; aspartate aminotransferase; guanosine; gene encoding fumarylacetoacetate hydrolase; gas chromatography mass spectrometry
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2013.10.021

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 14kb 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.754G>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.754G>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. •Target next-generation sequencing and bioinformatics were applied in this study.•A missense mutation was detected by next-generation sequencing in a pedigree.•The mutations c.754G>A and c.1177+1G>A were common pathogenic.•c.754G>A (p.Glu252Lys) is a first report of citrin deficiency in China.