title: Splicing mosaic of the myophosphorylase gene due to a silent mutation in McArdle disease.
abstract: The authors report the molecular findings in a patient with McArdle disease who harbored a silent polymorphism (K608K) in the myophosphorylase gene. cDNA studies demonstrated that this polymorphism leads to a severe mosaic alteration in mRNA splicing, including exon skipping, activation of cryptic splice-sites, and exon-intron reorganizations. These findings suggest that, in patients with McArdle disease in whom no pathogenic mutation has been found, any a priori silent polymorphism should be re-evaluated as a putative splicing mutation.
authors.affiliation: Centre d'Investigacions en Bioquímica y Biología Molecular, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: I
authors.initials: I
authors.lastname: Fernandez-Cadenas
authors.forename: A L
authors.initials: AL
authors.lastname: Andreu
authors.forename: J
authors.initials: J
authors.lastname: Gamez
authors.forename: R
authors.initials: R
authors.lastname: Gonzalo
authors.forename: M A
authors.initials: MA
authors.lastname: Martín
authors.forename: J C
authors.initials: JC
authors.lastname: Rubio
authors.forename: J
authors.initials: J
authors.lastname: Arenas
mesh_terms: D017398:Alternative Splicing / Q000235:genetics*; D024982:Glycogen Phosphorylase, Muscle Form / Q000096:biosynthesis / Q000235:genetics*; D006012:Glycogen Storage Disease Type V / Q000201:enzymology / Q000235:genetics*; D006801:Humans; D009154:Mutation; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000737:chemistry / Q000378:metabolism
chemical_list: D012333:RNA, Messenger; D024982:Glycogen Phosphorylase, Muscle Form