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Particular focus was placed on nonsense variants and their impact on gene expression. Functional assays were conducted to assess the ability of ataluren to restore SMC1A protein expression, correct transcriptional defects, and reduce genomic instability.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Transcriptomic alterations were strongly dependent on variant type, with nonsense variants causing the most profound gene expression changes. DEE85 and CdLS cell lines exhibited distinct transcriptional signatures. Treatment with ataluren led to successful restoration of SMC1A protein levels, partial correction of gene expression abnormalities, and a reduction in genomic instability in cells harboring nonsense variants.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Significance<\/jats:title>\n                    <jats:p>\n                      These findings demonstrate that\n                      <jats:italic>SMC1A<\/jats:italic>\n                      \u2010related epileptic encephalopathies are driven by variant\u2010specific molecular mechanisms and highlight the therapeutic promise of ataluren for DEE85. The study supports further development of precision medicine strategies targeting nonsense variants in\n                      <jats:italic>SMC1A<\/jats:italic>\n                      , with potential implications for improving diagnosis, treatment, and quality of life in affected individuals.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/epi.70150","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:59:55Z","timestamp":1772989195000},"page":"3185-3198","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Mutation type\u2010specific transcriptomic signatures and readthrough therapy rescue in\n                    <i>SMC1A<\/i>\n                    \u2010related developmental and epileptic encephalopathy"],"prefix":"10.1002","volume":"67","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1481-2101","authenticated-orcid":false,"given":"Maddalena","family":"Di Nardo","sequence":"first","affiliation":[{"name":"Institute of Biomedical Technologies, National Research Council  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6474-2079","authenticated-orcid":false,"given":"Francesca","family":"Sardina","sequence":"additional","affiliation":[{"name":"Institute of Molecular Biology and Pathology, National Research Council  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7731-8621","authenticated-orcid":false,"given":"Maria M.","family":"Pallotta","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Technologies, National Research Council  Pisa Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0674-6423","authenticated-orcid":false,"given":"I\u00f1igo","family":"Marcos\u2010Alcalde","sequence":"additional","affiliation":[{"name":"Molecular Modeling Group, Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas \u2010 Universidad Aut\u00f3noma de Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3131-729X","authenticated-orcid":false,"given":"Paulino","family":"G\u00f3mez\u2010Puertas","sequence":"additional","affiliation":[{"name":"Molecular Modeling Group, Centro de Biolog\u00eda Molecular Severo Ochoa, Consejo Superior de Investigaciones Cient\u00edficas \u2010 Universidad Aut\u00f3noma de Madrid  Madrid 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