Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing.

ABSTRACT: Diagnosis of the urea cycle disorder (USD) carbamoyl-phosphate synthetase 1 (CPS1) deficiency (CPS1D) based on only the measurements of biochemical intermediary metabolites is not sufficient to properly exclude other UCDs with similar symptoms. We report the first Korean CPS1D patient using whole exome sequencing (WES). A four-day-old female neonate presented with respiratory failure due to severe metabolic encephalopathy with hyperammonemia (1,690 ?mol/L; reference range, 11.2-48.2 ?mol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 ?mol/L; reference range, 131-710 ?mol/L) and glutamine (5,777 ?mol/L; reference range, 376-709 ?mol/L), whereas that of citrulline was decreased (2 ?mol/L; reference range, 10-45 ?mol/L). WES revealed compound heterozygous pathogenic variants in the CPS1 gene: one novel nonsense pathogenic variant of c.580C>T (p.Gln194*) and one known pathogenic frameshift pathogenic variant of c.1547delG (p.Gly516Alafs*5), which was previously reported in Japanese patients with CPS1D. We successfully applied WES to molecularly diagnose the first Korean patient with CPS1D in a clinical setting. This result supports the clinical applicability of WES for cost-effective molecular diagnosis of UCDs.

SUBMITTER: Choi R 

PROVIDER: S-EPMC5107619 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature