title: Dystrophin levels as low as 30% are sufficient to avoid muscular dystrophy in the human.
abstract: Mutations in the dystrophin gene give rise to Duchenne and Becker muscular dystrophies (DMD and BMD), in which both skeletal and cardiac muscles are affected, but also to X-linked dilated cardiomyopathy (XLDC), a condition characterised by exclusive cardiac involvement. XLDC patients with mutations at the 5' end of the gene typically have a cardiac specific severe transcriptional pathology, with absent dystrophin in the heart, while reduced levels of virtually normal dystrophin transcript and protein are present in the skeletal muscle. We now report the identification of a new XLDC family and the detailed characterisation of the levels of dystrophin protein present in skeletal muscle of this family, and of three previously studied XLDC families. We found that dystrophin levels comprised between 29% and 57% were sufficient to avoid muscle weakness in these XLDC families. This information will be of help for the development of therapeutic approaches aimed at restoring dystrophin levels sufficient to prevent the muscle pathology in DMD.
authors.affiliation: Dubowitz Neuromuscular Centre, Imperial College, Hammersmith Hospital, Du Cane Road, London W12 0NN, UK.
authors.forename: Marcella
authors.initials: M
authors.lastname: Neri
authors.forename: Silvia
authors.initials: S
authors.lastname: Torelli
authors.forename: Sue
authors.initials: S
authors.lastname: Brown
authors.forename: Isabella
authors.initials: I
authors.lastname: Ugo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Sabatelli
authors.forename: Luciano
authors.initials: L
authors.lastname: Merlini
authors.forename: Pietro
authors.initials: P
authors.lastname: Spitali
authors.forename: Paola
authors.initials: P
authors.lastname: Rimessi
authors.forename: Francesca
authors.initials: F
authors.lastname: Gualandi
authors.forename: Caroline
authors.initials: C
authors.lastname: Sewry
authors.forename: Alessandra
authors.initials: A
authors.lastname: Ferlini
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
mesh_terms: D000293:Adolescent; D000328:Adult; D002311:Cardiomyopathy, Dilated / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D004252:DNA Mutational Analysis; D016189:Dystrophin / Q000235:genetics*; D040181:Genetic Diseases, X-Linked / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000503:physiopathology; D020388:Muscular Dystrophy, Duchenne / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D009154:Mutation / Q000235:genetics; D009206:Myocardium / Q000378:metabolism / Q000473:pathology