LINEE CELLULARI DERIVATE DA PAZIENTI AFFETTI DA DISTROFIA FACIO-SCAPOLO-OMERALE (FSHD) DI TIPO 1 E 2 MOSTRANO LUNGO IL DIFFERENZIAMENTO MIOGENICO PROFILI DIVERSI DI ESPRESSIONE GENICA.

Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant disorder mainly associated with a contraction of the subtelomeric repeat D4Z4 on chromosome 4. The D4Z4 copy number is highly polymorphic in normal individuals ranging between 11-150 copies, whereas almost all FSHD patients (FSHD-1) carry fewer than 11 repeats. Nevertheless there is a subgroup of patients presenting clinical signs of disease without D4Z4 contraction (FSHD-2). Current hypothesis on FSHD-1 pathogenesis foresee the presence of an epigenetic molecular mechanism, but, how the contraction of D4Z4 array could determine alterations in chromatin structure and trigger transcriptional deregulation of target genes is not clear. Moreover the specific gene(s) responsible for FSHD phenotype have not yet been identified. To clarify some of these aspects, we used the Human GeneChip Exon 1.0 ST platform to analyze the global gene expression profiles of FSHD-1, FSHD-2 and controls proliferating myoblasts and the corresponding myotubes. Comparisons of normal and FSHD-1 myoblasts identified a greater number of deregulated genes in comparisons to normal and FSHD-1 myotubes, suggesting a defect in early stages of FSHD-1 differentiation. Moreover, the gene-expression profiles of FSHD-1 and FSHD-2 myoblast exhibited different categories of deregulated genes, demonstrating that different molecular mechanisms are responsible of the disease. The obtained results also suggest that miRNAs could be involved in the regulatory network of FSHD. Our approach provided new insights into the molecular mechanism of FSHD, allowing the identification of new candidate genes that may represent potential targets for clinical application