ClinVar

In a 27-year-old man with muscle weakness and cardiac arrhythmias associated with glycogen depletion (GSD15; 613507), Moslemi et al. (2010) identified compound heterozygosity for a 1-bp deletion (487delG) in exon 5 of the GYG1 gene, resulting in a frameshift and premature termination sequence at codon 167, and a 248C-T transition in exon 3 of the GYG1 gene, resulting in a thr83-to-met (T83M; 603942.0002) substitution at a highly conserved residue. The patient's unaffected mother was heterozygous for the deletion, and his unaffected father and 2 brothers were heterozygous for the missense mutation. Neither mutation was found in 200 control chromosomes of similar ancestry. Functional studies in Chinese hamster ovary (CHO) cells showed that recombinant wildtype glycogenin-1 was autoglucosylated, whereas recombinant T83M-mutant glycogenin-1 was not. RFLP analysis and sequencing demonstrated that the allele carrying the 487delG mutation was not expressed at the transcript level.