title: Leaky splicing mutation in the acid maltase gene is associated with delayed onset of glycogenosis type II.
abstract: An autosomal recessive deficiency of acid alpha-glucosidase (GAA), type II glycogenosis, is genetically and clinically heterogeneous. The discovery of an enzyme-inactivating genomic deletion of exon 18 in three unrelated genetic compound patients--two infants and an adult--provided a rare opportunity to analyze the effect of the second mutation in patients who displayed dramatically different phenotypes. A deletion of Lys-903 in one patient and a substitution of Arg for Leu-299 in another resulted in the fatal infantile form. In the adult, a T-to-G base change at position -13 of intron 1 resulted in alternatively spliced transcripts with deletion of exon 2, the location of the start codon. The low level of active enzyme (12% of normal) generated from the leakage of normally spliced mRNA sustained the patient to adult life.
authors.affiliation: Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institute of Health, Bethesda, MD 20892, USA.
authors.forename: C F
authors.initials: CF
authors.lastname: Boerkoel
authors.forename: R
authors.initials: R
authors.lastname: Exelbert
authors.forename: C
authors.initials: C
authors.lastname: Nicastri
authors.forename: R C
authors.initials: RC
authors.lastname: Nichols
authors.forename: F W
authors.initials: FW
authors.lastname: Miller
authors.forename: P H
authors.initials: PH
authors.lastname: Plotz
authors.forename: N
authors.initials: N
authors.lastname: Raben
mesh_terms: D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D005087:Glucan 1,4-alpha-Glucosidase / Q000235:genetics*; D006009:Glycogen Storage Disease Type II / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012326:RNA Splicing / Q000235:genetics*; D013997:Time Factors; D000520:alpha-Glucosidases
chemical_list: D000520:alpha-Glucosidases; D005087:Glucan 1,4-alpha-Glucosidase