title: Two mutations affecting the transport and maturation of lysosomal alpha-glucosidase in an adult case of glycogen storage disease type II.
abstract: The autosomal recessive glycogen storage disease type II is associated with a deficiency of lysosomal alpha-glucosidase (acid maltase). This paper reports on the mutations in the lysosomal alpha-glucosidase alleles of an adult patient. A G-1927 to A transition was discovered in exon 14 causing the substitution of Gly-643 by Arg and a second C-2173 to T transition in exon 15 resulting in the substitution of Arg-725 by Trp. Each of the mutations was located in a different allele. The mutations were introduced in the wild-type lysosomal alpha-glucosidase cDNA and expressed in COS cells. Both mutations had a similar effect. The synthesis of the mutant enzyme precursors was not disturbed but the intracellular transport and maturation were impaired. As a result there was an overall deficiency of catalytic activity.
authors.affiliation: Department of Cell Biology, Genetics and Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: M M
authors.initials: MM
authors.lastname: Hermans
authors.forename: M A
authors.initials: MA
authors.lastname: Kroos
authors.forename: E
authors.initials: E
authors.lastname: de Graaff
authors.forename: B A
authors.initials: BA
authors.lastname: Oostra
authors.forename: A J
authors.initials: AJ
authors.lastname: Reuser
mesh_terms: D000328:Adult; D000483:Alleles; D000818:Animals; D001483:Base Sequence; D001692:Biological Transport / Q000235:genetics; D002460:Cell Line; D004247:DNA; D005091:Exons; D006009:Glycogen Storage Disease Type II / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology*; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D014162:Transfection; D000520:alpha-Glucosidases / Q000235:genetics* / Q000378:metabolism
chemical_list: D004247:DNA; D000520:alpha-Glucosidases