title: Identification of six novel mutations in the acid alpha-glucosidase gene in three Spanish patients with infantile onset glycogen storage disease type II (Pompe disease).
abstract: Glycogen storage disease type II is an autosomal recessive muscle disorder due to deficiency of lysosomal acid alpha-glucosidase and the resulting intralysosomal accumulation of glycogen. We found six novel mutations in three Spanish classic infantile onset glycogen storage disease type II patients with involvement of both cardiac and skeletal muscle; three missense mutations (G219R, E262K, M408V), a nonsense mutation (Y191X), a donor splice site mutation (IVS18 +2gt>ga) and an in frame deletion of an asparagine residue (nt1408-1410). The missense mutations were not found in 100 normal chromosomes and therefore are not normal polymorphic variants. The splice site mutation was subsequently detected in an additional 'Spanish' infantile onset glycogen storage disease type II patient from El Salvador. Further studies will be required to determine if the IVS18 +2gt>ga splice site mutation might in fact be a relatively common Spanish mutation. Mutations among Spanish glycogen storage disease type II patients appear to be genetically heterogeneous and differ from common mutations in neighboring countries.
authors.affiliation: Division of Medical Genetics, Department of Medicine, New York University School of Medicine, 550 First Avenue, New York, NY 10016, USA.
authors.forename: Roberto
authors.initials: R
authors.lastname: Fernandez-Hojas
authors.forename: Maryann L
authors.initials: ML
authors.lastname: Huie
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
authors.forename: Carmen
authors.initials: C
authors.lastname: Dominguez
authors.forename: Manuel
authors.initials: M
authors.lastname: Roig
authors.forename: Diana
authors.initials: D
authors.lastname: Lopez-Coronas
authors.forename: Susana
authors.initials: S
authors.lastname: Teijeira
authors.forename: Kwame
authors.initials: K
authors.lastname: Anyane-Yeboa
authors.forename: Rochelle
authors.initials: R
authors.lastname: Hirschhorn
mesh_terms: D017668:Age of Onset; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001483:Base Sequence; D005091:Exons; D005260:Female; D006009:Glycogen Storage Disease Type II / Q000235:genetics*; D006801:Humans; D008247:Lysosomes / Q000201:enzymology; D008297:Male; D009154:Mutation; D016415:Sequence Alignment; D013030:Spain; D000520:alpha-Glucosidases / Q000235:genetics*
chemical_list: D000520:alpha-Glucosidases