title: Inspissated bile syndrome in an infant with citrin deficiency and congenital anomalies of the biliary tract and esophagus: identification and pathogenicity analysis of a novel SLC25A13 mutation with incomplete penetrance.
abstract: Biallelic mutations of the SLC25A13 gene result in citrin deficiency (CD) in humans. Neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) is the major CD phenotype in pediatrics; however, knowledge on its genotypic and phenotypic characteristics remains limited. The present study aimed to explore novel molecular and clinical characteristics of CD. An infant suspected to have NICCD as well as her parents were enrolled as the research subjects. SLC25A13 mutations were investigated using various methods, including cDNA cloning and sequencing. The pathogenicity of a novel mutation was analyzed bioinformatically and functionally with a yeast model. Both the infant and her father were heterozygous for c.2T>C and c.790G>A, while the mother was only a c.2T>C carrier. The novel c.790G>A mutation proved bioinformatically and functionally pathogenic. The infant had esophageal atresia and an accessory hepatic duct, along with bile plug formation confirmed by laparoscopic surgery. However, the father seemed to be healthy thus far. The findings of the present study enrich the genotypic and phenotypic characteristics of CD patients, and provided clinical and molecular evidence suggesting the possible non-penetrance of SLC25A13 mutations and the likely involvement of this gene in primitive foregut development during early embryonic life.
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Han-Shi
authors.initials: HS
authors.lastname: Zeng
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Shu-Tao
authors.initials: ST
authors.lastname: Zhao
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Mei
authors.initials: M
authors.lastname: Deng
authors.affiliation: Central Laboratory, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Zhan-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.affiliation: Medical Imaging Center, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Xiang-Ran
authors.initials: XR
authors.lastname: Cai
authors.affiliation: Department of Laboratory Science, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Feng-Ping
authors.initials: FP
authors.lastname: Chen
authors.affiliation: Department of Pediatrics, The First Affiliated Hospital, Jinan University, Guangzhou, Guangdong 510630, P.R. China.
authors.forename: Yuan-Zong
authors.initials: YZ
authors.lastname: Song
mesh_terms: D001659:Biliary Tract / Q000002:abnormalities*; D002135:Calcium-Binding Proteins / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D003001:Cloning, Molecular; D019295:Computational Biology; D000013:Congenital Abnormalities / Q000473:pathology*; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D004947:Esophagus / Q000002:abnormalities*; D005260:Female; D006801:Humans; D007223:Infant; D033681:Mitochondrial Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism; D020125:Mutation, Missense; D027361:Organic Anion Transporters / Q000097:blood / Q000172:deficiency* / Q000235:genetics; D019683:Penetrance; D010641:Phenotype; D017422:Sequence Analysis, DNA
chemical_list: D002135:Calcium-Binding Proteins; D018076:DNA, Complementary; D033681:Mitochondrial Membrane Transport Proteins; D027361:Organic Anion Transporters; C119629:SLC25A13 protein, human; C008822:citrin