A new rare mutation (691delCC/insAAA) in exon 17 of the PYGM gene causing McArdle disease.

Objective: To investigate the genetic effect of a new mutation found in exon 17 of the myophosphorylase (PYGM) gene as a cause of McArdle disease (also known as type 5 glycogenosis). Patients A Spanish patient with McArdle disease was screened for 3 common mutations in the PYGM gene (R49X, W797R, and G204S), as previously described. The patient was heterozygous for R49X.

Unusual clinical findings and Complex III deficiency in a family with myotonic dystrophy.

Myotonic dystrophy type 1 (DM1), an autosomal dominant disease characterized by a CTG expansion in the 3' region of the DMPK gene in chromosome 19, is a highly heterogeneous disease. In this study, we present a family with early onset-classical type DM, and a homogeneous phenotype highlighted by severe neuromuscular symptoms and mental dysfunction with subcortical-type dementia. Neuroradiological abnormalities included brain atrophy, white matter lesions, and basal ganglia calcifications.

Identification of six novel mutations in the acid alpha-glucosidase gene in three Spanish patients with infantile onset glycogen storage disease type II (Pompe disease).

Glycogen storage disease type II is an autosomal recessive muscle disorder due to deficiency of lysosomal acid alpha-glucosidase and the resulting intralysosomal accumulation of glycogen. We found six novel mutations in three Spanish classic infantile onset glycogen storage disease type II patients with involvement of both cardiac and skeletal muscle; three missense mutations (G219R, E262K, M408V), a nonsense mutation (Y191X), a donor splice site mutation (IVS18 +2gt>ga) and an in frame deletion of an asparagine residue (nt1408-1410). The missense mutations were not found in 100 normal chromosomes and therefore are not normal polymorphic variants.

Molecular heterogeneity of myophosphorylase deficiency (McArdle's disease): a genotype-phenotype correlation study.

We report on 54 Spanish patients with McArdle's disease from 40 unrelated families. Molecular analysis revealed that the most common R49X mutation was present in 70% of patients and 55% of alleles. The G204S mutation was less frequent and found in 14.

Autosomal dominant limb-girdle muscular dystrophy: a large kindred with evidence for anticipation.

Background: Fourteen genetically distinct forms of limb-girdle muscular dystrophy (LGMD) have been identified, including five types of autosomal dominant LGMD (AD-LGMD).

Objective: To describe clinical, histologic, and genetic features of a large Spanish kindred with LGMD and apparent autosomal dominant inheritance spanning five generations.

Method: The authors examined 61 members of the family; muscle biopsies were performed on five patients.