Novel Pathogenic Variant (c.580C>T) in the CPS1 Gene in a Newborn With Carbamoyl Phosphate Synthetase 1 Deficiency Identified by Whole Exome Sequencing.
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.
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Rihwa
R
Choi
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. nayadoo@hanmail.net.
Hyung Doo
HD
Park
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Mina
M
Yang
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Chang Seok
CS
Ki
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Soo Youn
SY
Lee
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Jong Won
JW
Kim
Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea.
Junghan
J
Song
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.
Yun Sil
YS
Chang
Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Samsung Biomedical Research Institute, Sungkyunkwan University School of Medicine, Seoul, Korea. ws123.park@samsung.com.
Won Soon
WS
Park
D001483:Base Sequence; D002222:Carbamoyl-Phosphate Synthase (Ammonia) / Q000737:chemistry / Q000235:genetics*; D020165:Carbamoyl-Phosphate Synthase I Deficiency Disease / Q000175:diagnosis / Q000235:genetics*; D018389:Codon, Nonsense; D005091:Exons; D005260:Female; D016368:Frameshift Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D007231:Infant, Newborn; D056910:Republic of Korea; D017422:Sequence Analysis, DNA; D056806:Urea Cycle Disorders, Inborn / Q000175:diagnosis
D018389:Codon, Nonsense; D002222:Carbamoyl-Phosphate Synthase (Ammonia)
CPS1; Carbamoyl-phosphate synthetase 1 deficiency; Hyperammonemia; Urea cycle disorders; Whole exome sequencing