title: Resolution of a mispaired secondary structure intermediate could account for a novel micro-insertion/deletion (387 insA/del 8 bp) in the PYGM gene causing McArdle's disease.
abstract: We report two siblings with McArdle's disease who are both compound heterozygotes for two non-identical frameshift mutations in the PYGM gene; a previously reported 753 delA in exon 18 and a novel 387 insA/del 8 bp in exon 10. The novel mutation is predicted to result in premature termination of translation 33 amino acids downstream of the site of mutation, potentially encoding a severely truncated protein of 419 amino acids instead of 841 amino acids. The complete lack of myophosphorylase activity observed in muscle derived from one sibling suggests that this mutation has deleterious functional consequences. The underlying mechanism of mutagenesis may have been slipped mispairing mediated by the formation of a Moebius loop-like secondary intermediate.
authors.affiliation: Centro de Investigación, Hospital 12 de Octubre, Madrid, Spain.
authors.forename: M A
authors.initials: MA
authors.lastname: Martín
authors.forename: J C
authors.initials: JC
authors.lastname: Rubio
authors.forename: A
authors.initials: A
authors.lastname: García
authors.forename: M A
authors.initials: MA
authors.lastname: Fernández
authors.forename: Y
authors.initials: Y
authors.lastname: Campos
authors.forename: M
authors.initials: M
authors.lastname: Krawczak
authors.forename: D N
authors.initials: DN
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: Arenas
mesh_terms: D000328:Adult; D001483:Base Sequence; D004252:DNA Mutational Analysis; D017353:Gene Deletion; D006012:Glycogen Storage Disease Type V / Q000201:enzymology / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D016254:Mutagenesis, Insertional; D009154:Mutation; D006005:Phosphorylases / Q000235:genetics*; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D006005:Phosphorylases