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Neuromolecular Med ; 15(3): 470-5, 2013 Sep.
Article in English | MEDLINE | ID: mdl-23653251

ABSTRACT

McArdle's disease, a glycogen storage disease type V, is caused by a deficiency of the enzyme myophosphorylase, encoded by the PYGM gene. Worldwide distribution of mutations has revealed interesting data about the prevalence of mutations and population migrations. Currently, more than 100 mutations in the PYGM gene have been described, with some recurrent mutations in the different populations. However, no molecular studies of McArdle's disease were reported in Brazilian patients. Here, we describe the clinical phenotype and genotype of 10 patients from 8 unrelated Brazilian families. Among the 10 patients (3 females, 7 males), eight presented with the typical phenotype, with exercise intolerance, cramps, and myalgia; one patient showed permanent muscle weakness; and one patient showed a mild phenotype. Molecular analysis identified 5 different mutations in the 8 families, both in homozygosis or compound heterozygosis state. Four of them had already been described (p.R50X, p.T692kfs30, p.K609K, and p.G455R), and one, pI513V, is a novel heterozygous mutation. The common nonsense p.R50X mutation was found in 6 of the 8 families, being therefore the commonest mutation in the Brazilian population as well. Other mutations previously reported in European patients were also found in the patients in this study, which was expected considering the European ancestry of the Brazilian population.


Subject(s)
Glycogen Phosphorylase, Muscle Form/genetics , Glycogen Storage Disease Type V/genetics , Mutation , Adolescent , Adult , Aged , Amino Acid Sequence , Biopsy , Brazil/epidemiology , Codon, Nonsense , Electromyography , Europe/ethnology , Exercise Tolerance , Female , Genotype , Glycogen Phosphorylase, Muscle Form/chemistry , Glycogen Phosphorylase, Muscle Form/deficiency , Glycogen Storage Disease Type V/ethnology , Humans , Male , Middle Aged , Molecular Sequence Data , Muscle, Skeletal/pathology , Muscle, Skeletal/physiopathology , Mutation, Missense , Myoglobinuria/genetics , Phenotype , Sequence Analysis, DNA , Young Adult
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