Identification and Characterization of a Novel Splice Site Mutation Associated with Glycogen Storage Disease Type VI in Two Unrelated Turkish Families

Introduction: Glycogen storage disease type VI (GSD VI) is a disorder of glycogen metabolism due to mutations in the PYGL gene. Patients with GSD VI usually present with hepatomegaly, recurrent hypoglycemia, and short stature. Results: We report on two non-related Turkish patients with a novel homozygous splice site variant, c.345G>A, which was shown to lead to exon 2 skipping of the PYGL-mRNA by exome and transcriptome analysis. According to an in silico analysis, deletion Arg82_Gln115del is predicted to impair protein stability and possibly AMP binding. Conclusion: GSD VI is a possibly underdiagnosed disorder, and in the era of next generation sequencing, more and more patients with variants of unknown significance in the PYGL-gene will be identified. Techniques, such as transcriptome analysis, are important tools to confirm the pathogenicity and to determine therapeutic measures based on genetic results.

Automated summary

The study reported novel homozygous splice site variants in two Turkish patients with GSD VI, leading to impaired protein stability. In the era of next generation sequencing, techniques like transcriptome analysis are crucial for confirming pathogenicity and determining personalized therapeutic measures based on genetic results.