A novel mutation (86insA) in the alpha-sarcoglycan-gene leads to severe childhood autosomal recessive muscular dystrophy

Introduction: Alpha-sarcoglycanopathy is an autosomal recessive muscular dystrophy. The clinical phenotype can vary from mild limb-girdle muscular dystrophy type 2 (LGMD2) to a severe Duchenne-like phenotype (SCARMD). The disease is caused by mutations in the alpha-sarcoglycan gene. We report a case of alpha-sarcoglycanopathy in an adult female patient with onset in the first decade of life and with Duchenne-like phenotype.

Methods: Presentation of clinical, immuno-histochemical and molecular genetic data.

Results: The patient is a 40-year-old female with no family history of neuromuscular disease. With 12 years she was unable to walk and was restricted to a wheelchair. At the age of 30 she received a tracheotomy for respiratory failure owing to weakness in her respiratory muscles. Her muscle biopsy specimen revealed dystrophic features. Immunohistochemical analysis demonstrated complete absence of alpha-sarcoglycan and reduced staining of beta and gamma-sarcoglycan. Antibodies against dystrophin were normal. Molecular analysis revealed a novel homozygous mutation in the alpha-sarcoglycan gene: 86 insA. The predicted consequence of this mutation is the introduction of a premature stop codon, which results in a total loss of alpha-sarcoglycan in the sarcolemma.

Conclusions: As shown by the clinical and immunohistochemical data, the mutation 86insA leads to a severe Duchenne-like muscular dystrophy. This finding confirms the pathogenic character of the mutation as well as its predicted consequences, namely the complete loss of alpha-sarcoglycan.

Keywords: alpha-sarcoglycan, muscular dystrophy, mutation, SCARMD, immunohistochemistry