[Clinical features and genetic analysis of a child with Congenital disorder of glycosylation due to novel variants of COG6 gene].

Abstract

Objective: To analyze the clinical characteristics of a child with Congenital disorder of glycosylation due to compound heterozygous variants of COG6 gene (COG6-CDG).

Methods: A child who was admitted to Xi'an Children's Hospital on January 10, 2023 was selected as the study subject. Clinical data were collected. Pathogenic variants were analyzed by whole exome sequencing, and candidate variants were verified by Sanger sequencing, in vitro experiments and bioinformatic analysis. This study was approved by the Medical Ethics Committee of Xi'an Children's Hospital (Ethics No. 20230101).

Results: The child, a 1-month-8-day-old male, was admitted for diarrhea and weight loss for one month. He had presented with cholestasis, diarrhea, facial dysmorphism, poor response, bilateral Simian crease, and brain atrophy. After discharge, he had continued to have high fever, feeding difficulty, and deceased finally. Whole exome sequencing results showed that he had harbored compound heterozygous variants of the COG6 gene, namely c.807delT (p.F269Lfs*37) and c.1746+1G>C (p.Gly565_Met582del). Sanger sequencing verified that the variants were inherited from his father and mother, respectively. In vitro experiments verified that the c.1746+1G>C variant could affect the mRNA splicing and produce a truncated protein, whilst the c.807delT variant could significantly reduce gene expression at both mRNA and protein levels. Based on the guidelines from the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG-AMP), the variants were classified as pathogenic (PVS1+PM3+PM2_Supporting) and likely pathogenic (PVS1+PM2_Supporting), respectively.

Conclusion: The c.807delT (p.F269Lfs*37) and c.1746+1G>C (p.Gly565_Met582del) compound heterozygous variants of the COG6 gene probably underlay the pathogenesis of this child. Above finding has enriched the mutational spectrum of COG6-CDG and provided a basis for the genetic counseling for this family.