Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing.
- Author:
Rihwa CHOI
1
;
Hyung Doo PARK
;
Mina YANG
;
Chang Seok KI
;
Soo Youn LEE
;
Jong Won KIM
;
Junghan SONG
;
Yun Sil CHANG
;
Won Soon PARK
Author Information
- Publication Type:Brief Communication ; Case Reports
- Keywords: Carbamoyl-phosphate synthetase 1 deficiency; CPS1; Hyperammonemia; Urea cycle disorders; Whole exome sequencing
- MeSH: Base Sequence; Carbamoyl-Phosphate Synthase (Ammonia)/chemistry/*genetics; Carbamoyl-Phosphate Synthase I Deficiency Disease/diagnosis/*genetics; Codon, Nonsense; Exons; Female; Frameshift Mutation; High-Throughput Nucleotide Sequencing; Humans; Infant, Newborn; Republic of Korea; Sequence Analysis, DNA; Urea Cycle Disorders, Inborn/diagnosis
- From:Annals of Laboratory Medicine 2017;37(1):58-62
- CountryRepublic of Korea
- Language:English
- 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 µmol/L; reference range, 11.2-48.2 µmol/L). Plasma amino acid analysis revealed markedly elevated levels of alanine (2,923 µmol/L; reference range, 131-710 µmol/L) and glutamine (5,777 µmol/L; reference range, 376-709 µmol/L), whereas that of citrulline was decreased (2 µmol/L; reference range, 10-45 µmol/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.
