title: The cell biology of disease: FSHD: copy number variations on the theme of muscular dystrophy.
abstract: In humans, copy number variations (CNVs) are a common source of phenotypic diversity and disease susceptibility. Facioscapulohumeral muscular dystrophy (FSHD) is an important genetic disease caused by CNVs. It is an autosomal-dominant myopathy caused by a reduction in the copy number of the D4Z4 macrosatellite repeat located at chromosome 4q35. Interestingly, the reduction of D4Z4 copy number is not sufficient by itself to cause FSHD. A number of epigenetic events appear to affect the severity of the disease, its rate of progression, and the distribution of muscle weakness. Indeed, recent findings suggest that virtually all levels of epigenetic regulation, from DNA methylation to higher order chromosomal architecture, are altered at the disease locus, causing the de-regulation of 4q35 gene expression and ultimately FSHD.
authors.affiliation: International PhD Program in Cellular and Molecular Biology, Vita-Salute San Raffaele University, 20132 Milan, Italy.
authors.forename: Daphne Selvaggia
authors.initials: DS
authors.lastname: Cabianca
authors.forename: Davide
authors.initials: D
authors.lastname: Gabellini
mesh_terms: D000818:Animals; D056915:DNA Copy Number Variations / Q000235:genetics*; D019175:DNA Methylation; D015870:Gene Expression; D006801:Humans; D020391:Muscular Dystrophy, Facioscapulohumeral / Q000235:genetics*; D020080:Tandem Repeat Sequences