biostudies-literatureUnknown36(1)Anwar SDysferlinopathies are debilitating autosomal recessive muscular dystrophies caused by mutations in the <i>DYSF</i> gene, encoding dysferlin, a protein crucial for sarcolemmal homeostasis and membrane resealing. Currently, no therapies exist for dysferlinopathies. Dysferlin features a modular structure with multiple calcium-dependent C2 lipid-binding domains. Clinical reports of mild, late-onset phenotypes suggest partial retention of functionality despite missing C2 domains, supporting exon-skipping therapies using antisense oligonucleotides (ASOs). In this study, we identified a patient-derived muscle cell line with a splice site mutation in <i>DYSF</i> intron 26, causing exon 26 exclusion, an out-of-frame transcript, and no detectable dysferlin protein. We hypothesized that skipping <i>DMolecular therapy. Nucleic acids102443https://www.ebi.ac.uk/biostudies/studies/S-EPMC11834094biostudies-literatureAntisense oligonucleotide-mediated exon 27 skipping restores dysferlin function in dysferlinopathy patient-derived muscle cells.PMC11834094Roshmi RRBigot AWoo SHaque USAnwar SArthur Lee JJDuddy WJMaruyama RYokota TfalseAntisense oligonucleotide-mediated exon 27 skipping restores dysferlin function in dysferlinopathy patient-derived muscle cells.Dysferlinopathies are debilitating autosomal recessive muscular dystrophies caused by mutations in the <i>DYSF</i> gene, encoding dysferlin, a protein crucial for sarcolemmal homeostasis and membrane resealing. Currently, no therapies exist for dysferlinopathies. Dysferlin features a modular structure with multiple calcium-dependent C2 lipid-binding domains. Clinical reports of mild, late-onset phenotypes suggest partial retention of functionality despite missing C2 domains, supporting exon-skipping therapies using antisense oligonucleotides (ASOs). In this study, we identified a patient-derived muscle cell line with a splice site mutation in <i>DYSF</i> intron 26, causing exon 26 exclusion, an out-of-frame transcript, and no detectable dysferlin protein. We hypothesized that skipping <i>D2025-01-01T00:00:00Z2025 Mar2025-04-03T23:16:54.328Z2025-04-03T23:16:54.328ZS-EPMC118340943996785210.1016/j.omtn.2024.102443