biostudies-literatureUnknown16(1)Strafella C<h4>Background</h4>Facioscapulohumeral dystrophy (FSHD) is a myopathy characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). The assessment of DNA methylation at two regions (DUX4-PAS and DR1) of D4Z4 locus proved to be an effective method to detect epigenetic signatures compatible with FSHD. The present study aims at validating the employment of this method into clinical practice and improving the protocol by refining the classification thresholds of 4qA/4qA patients. To this purpose, 218 subjects with clinical suspicion of FSHD collected in 2022-2023 were analyzed. Each participant underwent in parallel the traditional FSHD molecular testing (D4Z4 sizing) and the proposed methylation assay. The results provided by both analyses were compared to evaluClinical epigenetics148https://www.ebi.ac.uk/biostudies/studies/S-EPMC11520157biostudies-literatureIntegrating D4Z4 methylation analysis into clinical practice: improvement of FSHD molecular diagnosis through distinct thresholds for 4qA/4qA and 4qA/4qB patients.PMC11520157Primiano GMegalizzi DGerardi FStrafella CCascella RRodolico CPetillo RGadaleta GGragnani FFSHD Italian Clinical GroupMaioli MAMonforte MTasca GSiciliano GTorri FRisi BGrandis MVercelli LRavera BSansone VPane MZampatti SScutifero MGioiosa VPugliese ASancricca CCaria FFrezza EFilosto MCarraro EFrongia AManfroi EProietti Piorgo ECasali CPetrucci APassamano LPrevitali SCTrastulli GPennisi EMTorchia EMassa RGaribaldi MRicci GGiardina EMongini TEBortolani SRicci EMandich PColantoni LTufano LCaltagirone CPolitano LfalseIntegrating D4Z4 methylation analysis into clinical practice: improvement of FSHD molecular diagnosis through distinct thresholds for 4qA/4qA and 4qA/4qB patients.<h4>Background</h4>Facioscapulohumeral dystrophy (FSHD) is a myopathy characterized by the loss of repressive epigenetic features affecting the D4Z4 locus (4q35). The assessment of DNA methylation at two regions (DUX4-PAS and DR1) of D4Z4 locus proved to be an effective method to detect epigenetic signatures compatible with FSHD. The present study aims at validating the employment of this method into clinical practice and improving the protocol by refining the classification thresholds of 4qA/4qA patients. To this purpose, 218 subjects with clinical suspicion of FSHD collected in 2022-2023 were analyzed. Each participant underwent in parallel the traditional FSHD molecular testing (D4Z4 sizing) and the proposed methylation assay. The results provided by both analyses were compared to evalu2024-01-01T00:00:00Z2024 Oct2026-07-15T15:31:26.559Z2025-04-19T18:13:50.194ZS-EPMC115201573943890010.1186/s13148-024-01747-2