Exome Sequencing Identifies A Novel Mutation In The Gaa Gene In A Patient With Glycogen Storage Disease Type Ii

Glycogen storage disease is a group of inherited metabolic diseases resulting from a defect in the synthesis or degradation of glycogen. Glycogen storage disease type II is an autosomal recessive disorder caused by a deficiency of acid alpha-glucosidase, and the subsequent intralysosomal accumulation of glycogen, predominantly in the skeletal muscles. This article aimed to definitively diagnose a Chinese myopathy family, and to find the causative mutations of myopathy. Exome sequencing, with its high chromosomal coverage and accuracy, has been successfully used to identify pathogenic mutations. Exome sequencing followed by Sanger sequencing was performed for a family with myopathy to screen for the causative mutations described in the present study. Results: Two compound heterozygous mutations, c.2236insT and c.2238G>C (p. Trp746Cys), were identified at codon 746 on exon 16 of the GM gene for the Chinese myopathy family. The patient was diagnosed with glycogen storage disease type II. The c.2236insT is a novel frameshift mutation predicted to truncate the distal C-terminal domain of acid alpha glucosidase. The c.2236insT variant is more severe compared with the mild p.Trp746Cys mutation. The current study suggests that exome sequencing is a powerful tool to find causative mutations in patients with myopathy. The novel c.2236insT mutation expands the genetic spectrum of glycogen storage disease type II, so it is helpful for genetic diagnosis.