title: Molecular and clinical study of McArdle's disease in a cohort of 123 European patients. Identification of 20 novel mutations.
abstract: McArdle's disease is the most common muscle glycogenosis. It is caused by the deficiency of myophosphorylase, encoded by the PYGM gene. We studied 123 patients previously diagnosed with McArdle's disease and we identified 20 novel mutations (10 missense and 3 nonsense mutations, 3 small deletions, 2 gross deletions and 2 small insertions). Most patients of this cohort belong to Spanish and French populations. This allowed us to determine the differences between the allelic frequencies of the common mutations R50X and G205S of these populations. The R50X has an allelic frequency in this cohort of about 61.7%, being 68.5% in French and 53.7% in Spanish patients. The G205S had a higher allelic frequency in the Spanish (10.2%) than in the French population (3.2%). Moreover, a clinical study of 91 patients was performed to establish both genotype-phenotype correlation and gender influence in the severity of the disease. We conclude that no genotype-phenotype correlation is evident and that no gender effect is related to the phenotype.
authors.affiliation: Department of Pathology and Neuropathology, University Hospital of Vigo, Meixoeiro, Vigo, Spain.
authors.forename: Irene
authors.initials: I
authors.lastname: Vieitez
authors.forename: Susana
authors.initials: S
authors.lastname: Teijeira
authors.forename: Jose M
authors.initials: JM
authors.lastname: Fernandez
authors.forename: Beatriz
authors.initials: B
authors.lastname: San Millan
authors.forename: Sara
authors.initials: S
authors.lastname: Miranda
authors.forename: Saida
authors.initials: S
authors.lastname: Ortolano
authors.forename: Sarah
authors.initials: S
authors.lastname: Louis
authors.forename: Pascal
authors.initials: P
authors.lastname: Laforet
authors.forename: Carmen
authors.initials: C
authors.lastname: Navarro
mesh_terms: D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005602:France / Q000453:epidemiology; D005787:Gene Frequency; D056726:Genetic Association Studies; D005838:Genotype; D024982:Glycogen Phosphorylase, Muscle Form / Q000172:deficiency / Q000235:genetics*; D006012:Glycogen Storage Disease Type V / Q000175:diagnosis / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010641:Phenotype; D013030:Spain / Q000453:epidemiology
chemical_list: D024982:Glycogen Phosphorylase, Muscle Form