Patients with glycogen storage disease type II (GSDII, Pompe disease) suffer from progressive muscle weakness due to acid α-glucosidase deficiency. The disease is inherited as an autosomal recessive trait with a spectrum of clinical phenotypes. We have investigated 29 cases of GSDII and thereby identified 55 pathogenic mutations of the acid α-glucosidase gene (GAA) encoding acid maltase. There were 34 different mutations identified, 22 of which were novel. All of the missense mutations and two other mutations with an unpredictable effect on acid α-glucosidase synthesis and function were transiently expressed in COS cells. The effect of a novel splice-site mutation was investigated by real-time PCR analysis. The outcome of our analysis underscores the notion that the clinical phenotype of GSDII is largely dictated by the nature of the mutations in the GAA alleles. This genotype-phenotype correlation makes DNA analysis a valuable tool to help predict the clinical course of the disease.

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Human Mutation
Department of Clinical Genetics

Hermans, M., van Leenen, D., Kroos, M., Beesley, C., van der Ploeg, A., Sakuraba, H., … Reuser, A. (2004). Twenty-Two Novel Mutations in the Lysosomal α-Glucosidase Gene (GAA) Underscore the Genotype-Phenotype Correlation in Glycogen Storage Disease Type II. Human Mutation, 23(1), 47–56. doi:10.1002/humu.10286