Full Description
The term "muscular dystrophy" (MD) describes a group of primary genetic disorders of muscle that often have a distinctive and recognizable clinical p- notype, accompanied by characteristic, but frequently not pathognomonic, pathological features. Research into the molecular basis of the MDs by a c- bination of positional cloning and candidate gene analysis has provided the basis for a reclassification of these disorders, with genetic and protein data augmenting traditional clinically based nomenclature. These findings have brought insights into the molecular pathogenesis of MD, with an increasing number of potential pathways involved in arriving at a dystrophic phenotype. Some common themes can be recognized, however, including the involvement of five members of the dystrophin-associated complex (dystrophin and four sarcoglycans) in different types of MD, and the involvement of two nuclear envelope proteins in producing an Emery-Dreifuss MD phenotype. Other d- ease-associated genes appear to cause MD in a completely unrelated way, such as the involvement of calpain 3 in a form of limb-girdle muscular dystrophy. Section 1 of Muscular Dystrophy: Methods and Protocols reviews tra- tional strategies used to identify MDs. Meantime, techniques developed as a result of the research strategies described previously have become an integral part of the management of many patients with MD and their families, and these techniques are addressed in Sections 2 (DNA-based tests) and 3 (p- tein-based analyses). The continued effort to translate this enhanced und- standing into a molecular cure or treatment for MD is reviewed in Section 4.
Contents
Background.- Application of Molecular Methodologies in Muscular Dystrophies.- Clinical Examination as a Tool for Diagnosis.- Histopathological Diagnosis of Muscular Dystrophies.- Serum Creatine Kinase in Progressive Muscular Dystrophies.- The molecular approach.- Deletion and Duplication Analysis in Males Affected with Duchenne or Becker Muscular Dystrophy.- Point Mutation Detection in the Dystrophin Gene.- DNA-Based Techniques for Detection of Carriers of Duchenne and Becker Muscular Dystrophy.- Fluorescence In Situ Hybridization Analysis for Carrier Detection in Duchenne/Becker Muscular Dystrophy.- DNA- Based Prenatal Diagnosis for Duchenne and Becker Muscular Dystrophy.- Molecular Diagnosis and Genetic Counseling of the Manifesting Carrier of Duchenne Muscular Dystrophy.- Mutation Analysis of X-Linked Emery-Dreifuss Muscular Dystrophy Gene.- Analysis of LAMA2 Gene in Merosin- Deficient Congenital Dystrophy.- ?-Sarcoglycan Mutations.- Mutation Detection in ?- and ?-Sarcoglycan (LGMD2E and LGMD2C).- Mutation Analysis in ?-Sarcoglycan (LGMD2F).- Molecular Diagnosis of Calpainopathies.- Molecular Investigation of LGMD2B-Haplotype Analysis and Mutation Screening.- Molecular Analysis of Facioscapulohumeral Muscular Dystrophy (FSHD1).- Protein Analysis in the Muscular Dystrophies.- Analysis of Protein Expression in Muscular Dystrophies.- Immunological Reagents and Amplification Systems.- Immunocytochemical Analysis.- Multiplex Western Blot Analysis of Muscular Dystrophy Proteins.- Fetal Muscle Biopsy.- Use of Animal Models to Understand Human Muscular Dystrophy.- Options for Development of Gene-Based Therapy for Muscular Dystrophy.
