title: Identification of a point mutation in the human lysosomal alpha-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 alpha-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 alpha-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 alpha-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.
authors.affiliation: Department of Cell Biology & Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Hermans
authors.forename: E
authors.initials: E
authors.lastname: de Graaff
authors.forename: M A
authors.initials: MA
authors.lastname: Kroos
authors.forename: H A
authors.initials: HA
authors.lastname: Wisselaar
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: A J
authors.initials: AJ
authors.lastname: Reuser
mesh_terms: D000483:Alleles; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004247:DNA / Q000032:analysis; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D015870:Gene Expression; D006009:Glycogen Storage Disease Type II / Q000209:etiology / Q000235:genetics*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D014162:Transfection; D000520:alpha-Glucosidases / Q000235:genetics*
chemical_list: D004247:DNA; C042059:glucosidase I; D000520:alpha-Glucosidases