{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T21:27:39Z","timestamp":1791235659252,"version":"4.1.0"},"reference-count":103,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T00:00:00Z","timestamp":1709164800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>To review the clinical characteristics and effect of treatment in patients with spinal muscular atrophy (SMA) and three copies of the <jats:italic>SMN2<\/jats:italic> gene.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted a literature search in October 2022 to identify English-language clinical research on SMA that included <jats:italic>SMN2<\/jats:italic> copy number according to PRISMA guidelines.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Our search identified 44 studies examining the impact of three <jats:italic>SMN2<\/jats:italic> copies on clinical characteristics (21 on phenotype, 13 on natural history, and 15 on functional status and other signs\/symptoms). In children with type I SMA or presymptomatic infants with an <jats:italic>SMN1<\/jats:italic> deletion, three <jats:italic>SMN2<\/jats:italic> copies was associated with later symptom onset, slower decline in motor function and longer survival compared with two <jats:italic>SMN2<\/jats:italic> copies. In patients with SMA type II or III, three <jats:italic>SMN2<\/jats:italic> copies is associated with earlier symptom onset, loss of ambulation, and ventilator dependence compared with four <jats:italic>SMN2<\/jats:italic> copies. Eleven studies examined treatment effects with nusinersen (nine studies), onasemnogene abeparvovec (one study), and a range of treatments (one study) in patients with three <jats:italic>SMN2<\/jats:italic> copies. In presymptomatic infants, early treatment delayed the onset of symptoms and maintained motor function in those with three <jats:italic>SMN2<\/jats:italic> copies. The impact of copy number on treatment response in symptomatic patients is still unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p><jats:italic>SMN2<\/jats:italic> copy number is strongly correlated with SMA phenotype in patients with <jats:italic>SMN1<\/jats:italic> deletion, while no correlation was found in patients with an <jats:italic>SMN1<\/jats:italic> mutation. Patients with three <jats:italic>SMN2<\/jats:italic> copies show a highly variable clinical phenotype. Early initiation of treatment is highly effective in presymptomatic patients with three <jats:italic>SMN2<\/jats:italic> copies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fneur.2024.1308296","type":"journal-article","created":{"date-parts":[[2024,2,29]],"date-time":"2024-02-29T05:24:52Z","timestamp":1709184292000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":27,"title":["The impact of three SMN2 gene copies on clinical characteristics and effect of disease-modifying treatment in patients with spinal muscular atrophy: a systematic literature review"],"prefix":"10.3389","volume":"15","author":[{"given":"Claudia","family":"Dosi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Riccardo","family":"Masson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,29]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1377","DOI":"10.3390\/genes14071377","article-title":"Spinal muscular atrophy treatment in patients identified by Newborn screening-a systematic review","volume":"14","author":"Aragon-Gawinska","year":"2023","journal-title":"Genes"},{"key":"ref2","year":"2023"},{"key":"ref3","article-title":"Spinal muscular atrophy","volume-title":"GeneReviews\u00ae","author":"Prior","year":"2000"},{"key":"ref4","doi-asserted-by":"publisher","first-page":"290","DOI":"10.1007\/s13311-014-0314-x","article-title":"The genetics of spinal muscular atrophy: progress and 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