Open AccessMolecular, biochemical, and clinical analyses of five patients with carbamoyl phosphate synthetase 1 deficiency
Author(s) -
Fan Lijuan,
Zhao Jing,
Jiang Li,
Xie Lingling,
Ma Jiannan,
Li Xiujuan,
Cheng Min
Publication year - 2020
Publication title -
journal of clinical laboratory analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.536
H-Index - 50
eISSN - 1098-2825
pISSN - 0887-8013
DOI - 10.1002/jcla.23124
Subject(s) - missense mutation , sanger sequencing , carbamoyl phosphate synthetase , in silico , mutation , compound heterozygosity , gene , genetics , urea cycle , biology , gene mutation , microbiology and biotechnology , amino acid , arginine
Background Carbamoyl phosphate synthetase 1 deficiency (CPS1D) is a rare urea cycle disorder. The aim of this study was to present the clinical findings, management, biochemical data, molecular genetic analysis, and short‐term prognosis of five children with CPS1D. Methods The information of five CPS1D patients was retrospectively studied. We used targeted next‐generation sequencing to identify carbamoyl phosphate synthetase 1 ( CPS1 ) variants in patients suspected to have CPS1D. Candidate mutations were validated by Sanger sequencing. In silico and structure analyses were processed for the pathogenicity predictions of the identified mutations. Results The patients had typically clinical manifestations and biochemical data of CPS1D. Genetic analysis revealed nine mutations in the CPS1 gene, including recurrence of c.1145C > T, five of which were firstly reported. Seven mutations were missense changes, while the remaining two were predicted to create premature stop codons. In silico and structure analyses showed that these genetic lesions were predicted to affect the function or stability of the enzyme. Conclusion We reported five cases of CPS1D. Five novel mutations of CPS1 gene were found. Mutations of CPS1 have private nature, and most of them are missense compound heterozygous. The mutation affecting residue predicted to interfere the catalytic sites, the internal tunnel, or the regulatory domain results in severe phenotype.