Strategy for mutation analysis in the autosomal recessive limb-girdle muscular dystrophies

We describe a strategy for molecular diagnosis in the autosomal recessive L imb-girdle muscular dystrophies, a highly heterogeneous group of inherited muscle-wasting diseases. Genetic mutation analysis is directed by immunoana lysis of muscle biopsies using antibodies against a panel of muscular dystr ophy-associated proteins. Performing the molecular analysis in this way gre atly increases the chance that mutations will be found in the first gene ex amined. The use of this strategy can significantly decrease the time involv ed in determining the genetic fault in a patient with a clinical diagnosis of recessive limb-girdle muscular dystrophy, as well as having a feedback e ffect, which is useful in helping clinicians to identify subtle clinical di fferences between the subtypes of the disease. The use of this approach has so far helped us to identify mutations in ten sarcoglycanopathy (limb-gird le muscular dystrophy 2C-2F) patients, and seven calpainopathy (Limb-girdle muscular dystrophy 2A) patients. (C) 2000 Elsevier Science B.V. All rights reserved.