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Digital archive of theses discussed at the University of Pisa

 

Thesis etd-10222023-213027


Thesis type
Tesi di specializzazione (4 anni)
Author
TORRI, FRANCESCA
URN
etd-10222023-213027
Thesis title
Clinical variability and molecular complexity of FSHD: relevance of deep phenotyping and comprehensive genetics in characterizing atypical clinical cases
Department
MEDICINA CLINICA E SPERIMENTALE
Course of study
NEUROLOGIA
Supervisors
relatore Prof. Siciliano, Gabriele
correlatore Dott.ssa Ricci, Giulia
Keywords
  • methylation
  • whole exome sequencing
  • deep phenotyping
  • muscular dystrophy
  • fshd
Graduation session start date
07/11/2023
Availability
Withheld
Release date
07/11/2026
Summary
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.
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