• methylation
• whole exome sequencing
• deep phenotyping
• muscular dystrophy
• fshd

Facioscapulohumeral muscular dystrophy (FSHD) is one of the most common forms of muscular dystrophy overall. While evidence is growing about phenotypic variability and possible different disease courses, knowledge of pathophysiologic mechanisms underlying those differences is still far from comprehensive. As clinical trials are finally approaching also for FSHD, understanding of the interplaying factors determining disease course, phenotypic characterization of patients, and choosing appropriate outcome measures is crucial. The aim of this study was to perform a comprehensive genetic characterization, through DNA methylation levels analysis and Whole Exome Sequencing, on a selected cohort of FSHD patients displaying atypical phenotypes, both sporadic and familial. In our cohort, methylation levels display a variable relation to disease phenotype and other disease-causing mutations, or disease-modifying genes, have been found. Evidence coming from this analysis further supports the need to perform a detailed phenotypic characterization of DRAs carriers in order to deepen our understanding on the molecular landscape of FSHD.