Two novel compound heterozygous mutations in NGLY1as a cause of congenital disorder of deglycosylation: a case presentation

BMC Med Genet. 2020 Jun 23;21(1):135. doi: 10.1186/s12881-020-01067-1.


Background: NGLY1-related congenital disorder of deglycosylation (NGLY1-CDDG) is a multisystemic neurodevelopmental disorder in which affected individuals show developmental delay, epilepsy, intellectual disability, abnormal liver function, and poor growth. This study presents a 10-month-old female infant with elevated liver transaminases, developmental delay, epilepsy (subclinical seizures), and constipation who possesses two compound heterozygous mutations in NGLY1.

Case presentation: The proband was admitted to the Department of Gastroenterology, Children's Hospital of Soochow University, with elevated liver transaminases. She had a history of intrauterine growth retardation and exhibited elevated transaminases, global developmental delay, seizures and light constipation during early infancy. Whole-exome sequencing (WES) and Sanger sequencing revealed two compound heterozygous mutations in NGLY1 that had been inherited in an autosomal recessive manner from her parents. One was a termination mutation, c.1168C > T (p.R390*), and the other was a missense mutation, c.1156G > T (p.D386Y). NGLY1-CDDG is a rare disorder, with a few dozen cases. The two mutations of this proband has not been previously identified.

Conclusions: This study investigated a Chinese proband with NGLY1-CDDG born from healthy parents who was studied using WES and Sanger sequencing to identify the causative mutations. We identified two novel compound heterozygous mutations in NGLY1, c.1168C > T (p.R390*)/c.1156G > T (p.D386Y), which are probably causative of disease.

Keywords: Congenital disorder of deglycosylation; Constipation; Elevated transaminase developmental delay; NGLY1; Seizure.

Publication types

  • Case Reports

MeSH terms

  • Amino Acid Sequence
  • Base Sequence
  • Brain / diagnostic imaging
  • Brain / pathology
  • Congenital Disorders of Glycosylation / enzymology*
  • Congenital Disorders of Glycosylation / genetics*
  • Female
  • Heterozygote
  • Humans
  • Infant
  • Infant, Newborn
  • Magnetic Resonance Imaging
  • Mutation / genetics*
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / chemistry
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / deficiency*
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase / genetics


  • NGLY1 protein, human
  • Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase

Supplementary concepts

  • NGLY1 deficiency