Hannes Erdmann (München / DE), Florentine Scharf (München / DE), Dr. Stefanie Gehling (München / DE), Dr. Anna Benet-Pagès (Neuherberg / DE; München / DE), Dr. Sybille Jakubiczka (Magdeburg / DE), Dr. Kerstin Becker (München / DE), Dr. Maria Seipelt (Marburg / DE), Dr. med Felix Kleefeld (Berlin / DE), Dr. Karl Christian Knop (Hamburg / DE), Dr. Eva-Christina Prott (Wuppertal / DE), Dr. Miriam Hiebeler (München / DE), Dr. Federica Montagnese (München / DE), Dr. Dieter Gläser (Neu-Ulm / DE), Prof. Dr. Matthias Vorgerd (Bochum / DE), Univ.-Prof. Dr. med. Tim Hagenacker (Essen / DE), Prof. Dr. Maggie C. Walter (München / DE), Priv.-Doz. Dr. med. Peter Reilich (München / DE), Dr. Teresa Neuhann (München / DE), Prof. Dr. Martin Zenker (Magdeburg / DE), Prof. Dr. Elke Holinski-Feder (München / DE), Prof. Dr. med. Benedikt Schoser (München / DE), Prof. Dr. Angela Abicht (München / DE)
Abstract-Text (inkl. Referenzen)
Genetic diagnosis of facioscapulohumeral muscular dystrophy (FSHD) remains a challenge in clinical practice due to incomplete penetrance and epistatic effects of the underlying genetic parameters, which also hinders prediction of clinical severity. We implemented a high-throughput methylation profile analysis for the diagnosis of FSHD based on determining the global methylation level of the D4Z4 repeat array and the regional methylation of the most distal repeat unit by combining bisulfite conversion with next-generation sequencing (NGS) and a bioinformatics pipeline. We analyzed a cohort of 148 patients with FSHD phenotype and compared the epigenetic parameters to genetic ones of conventional genetic testing. In addition, we studied the correlation of distal methylation level with age-corrected clinical severity and age at disease onset in FSHD patients. Our study shows that methylation profiles are reliable parameters for the diagnosis of FSHD, allowing discrimination between FSHD patients and healthy individuals, while simultaneously distinguishing FSHD1 and FSHD2. The strong correlation observed between methylation level and age-corrected clinical severity indicates that the methylation level can serve as a biomarker for disease severity and as a prognostic marker. Our findings indicate that epigenetic parameters rather than genetic parameters represent FSHD disease status and may serve as a valuable biomarker for disease status.