The medical genetics of dystrophinopathies: Molecular genetic diagnosis and its impact on clinical practice

Abstract A large variety of mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies, diseases affecting predominantly the striated muscles (skeletal and cardiac). Rare mutations also account for the allelic disorder isolated X-linked dilated cardiomyopathy. Dystrophin protein...

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Bibliographic Details
Published in:Neuromuscular disorders : NMD 2013-01, Vol.23 (1), p.4-14
Main Authors: Ferlini, Alessandra, Neri, Marcella, Gualandi, Francesca
Format: Article
Language:English
Subjects:
Duchenne and Becker muscular dystrophies
Dystrophin
Dystrophin - genetics
Female
Genetic Testing - methods
Genotype
Genotype phenotype correlation
Humans
Male
Molecular Biology - methods
Molecular genetics
Muscular Dystrophies - diagnosis
Muscular Dystrophies - genetics
Mutation - genetics
Mutations
Neurology
Pedigree
Phenotype
Practice Patterns, Physicians' - trends
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Summary:Abstract A large variety of mutations in the dystrophin gene cause Duchenne and Becker muscular dystrophies, diseases affecting predominantly the striated muscles (skeletal and cardiac). Rare mutations also account for the allelic disorder isolated X-linked dilated cardiomyopathy. Dystrophin protein is encoded by a huge gene located on the X chromosome and the understanding of its complex genomic architecture has unraveled general key functions in gene expression regulation. Dystrophin also exists as a number of other tissue specific isoforms, some exclusively or predominantly expressed in the brain and/or in other tissues. Genotype definition of the dystrophin gene in patients with dystrophinopathies has taught us much about functionally important domains of the protein itself and has also provided insights regarding several regulatory mechanisms governing the gene expression profile. This review focuses on the current understanding of the dystrophin mutations heterogeneity, genotype-phenotype correlations, as well as interpretation of the functional significance of mutations that often require non routine genetic studies. It also explores the impact of genetic diagnosis on clinical definition and on the discovery of biomarkers and personalized therapies. Our aim is to offer an overview of the medical genetic approach on the dystrophin gene and dystrophinopathies with implications for clinical practice and therapeutic perspectives.
ISSN:0960-8966
1873-2364
DOI:10.1016/j.nmd.2012.09.002