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

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

Tejashwini Vittal Kumar  1 , Meenakshi Bhat  2   3 , Sanjeeva Ghanti Narayanachar  3 , Vinu Narayan  2 , Ambika K Srikanth  1 , Swathi Anikar  1 , Swathi Shetty  1
Affiliations

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

Tejashwini Vittal Kumar et al. PLoS One. .

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.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Topology of (a) G6Pase-α enzyme and (b) G6PT enzyme showing all variations identified in this study.
Fig 2
Fig 2. Distribution of identified pathogenic variants across the AGL gene and its domains, *-novel variations.
See this image and copyright information in PMC

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