Molecular and clinical profiling in a large cohort of Asian Indians with glycogen storage disorders

PLoS One. 2022 Jul 14;17(7):e0270373. doi: 10.1371/journal.pone.0270373. eCollection 2022.

Abstract

Glycogen storage disorders occur due to enzyme deficiencies in the glycogenolysis and gluconeogenesis pathway, encoded by 26 genes. GSD's present with overlapping phenotypes with variable severity. In this series, 57 individuals were molecularly confirmed for 7 GSD subtypes and their demographic data, clinical profiles and genotype-phenotype co-relations are studied. Genomic DNA from venous blood samples was isolated from clinically affected individuals. Targeted gene panel sequencing covering 23 genes and Sanger sequencing were employed. Various bioinformatic tools were used to predict pathogenicity for new variations. Close parental consanguinity was seen in 76%. Forty-nine pathogenic variations were detected of which 27 were novel. Variations were spread across GSDIa, Ib, III, VI, IXa, b and c. The largest subgroup was GSDIII in 28 individuals with 24 variations (12 novel) in AGL. The 1620+1G>C intronic variation was observed in 5 with GSDVI (PYGL). A total of eleven GSDIX are described with the first Indian report of type IXb. This is the largest study of GSDs from India. High levels of consanguinity in the local population and employment of targeted sequencing panels accounted for the range of GSDs reported here.

MeSH terms

  • Asian People
  • Glycogen
  • Glycogen Storage Disease Type I*
  • Glycogen Storage Disease*
  • Humans
  • Mutation

Substances

  • Glycogen

Grants and funding

The author(s) received no specific funding for this work.