Identification of a point mutation in the human lysosomal α-glucosidase gene causing infantile glycogenosis type II

Abstract Two patients in a consanguineous Indian family with infantile glycogenosis type II were found to have a G to A transition in exon 11 of the human lysosomal α-glucosidase gene. Both patients were homozygous and both parents were heterozygous for the mutant allele. The mutation causes a Glu to Lys substitution at amino acid position 521, just three amino acids downstream from the catalytic site at Asp-518. The mutation was introduced in wild type lysosomal α-glucosidase cDNA and the mutant construct was expressed in vitro and in vivo . The Glu to Lys substitution is proven to account for the abnormal physical properties of the patients lysosomal α-glucosidase precursor and to prevent the formation of catalytically active enzyme. In homozygous form it leads to the severe infantile phenotype of glycogenosis type II.