From proteins to genes: immunoanalysis in the diagnosis of muscular dystrophies

The term muscular dystrophies (MDs) refers to a large group of genetically inherited disorders characterised by weakness and wasting of skeletal muscle. The subclassification is based on mode of inheritance, age of onset and distribution of muscles affected. Progress made in the past 25 years has enabled the discovery of new causative genetic defects with many novel proteins involved in MD (an updated list of MDs and responsible genes can be found at http://www.musclegenetable.org webcite). Despite remarkable advances, this work is not yet complete, and although a large number of genes have been identified, a considerable number of patients still remain undiagnosed. Although a cure for most MDs is not yet available, an accurate diagnosis is key for natural history studies and to establish priorities for medical management, therapy and genetic counselling. Physical examination to determine the distribution of symptoms, together with medical and family history is central, but often the underlying genetic defect cannot be conclusively recognised on the basis of clinical information only. Indeed, differential diagnosis has to take into account the overlap of clinical features in different forms of MD and the heterogeneity in clinical presentation for many of the genes involved. Searching for gene mutations is the diagnostic gold standard but despite the rapidly evolving sequencing technologies, the analysis of multiple genes is still costly and time consuming and classification of gene mutations as pathogenic remains considerably challenging.A wide range of laboratory tests aid in the diagnostic process. Serum level of creatine kinase (CK) is a sensitive parameter of muscle damage. The degree of CK elevation is variable in different MDs and it can give an approximate indication of the type of disorder [1]. Electromyography enables differentiation between myopathic and neurogenic processes. Muscle magnetic resonance imaging, used to determine patterns of muscle involveme