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Multivariable models were used to explore prognostic modifiers.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In 144 patients (from 88 families), 29 mutations (26 missense, 2 deletion\/insertion and 1 frameshift) were found in all five exons of\n                      <jats:italic>SOD1<\/jats:italic>\n                      , including seven novel mutations. A total of 2.6% of ALS patients (including 17.7% familial and 1.3% sporadic) were estimated to carry\n                      <jats:italic>SOD1<\/jats:italic>\n                      mutations. The frequency of this mutation varied considerably among regions, due to founder events. The most frequent mutation was p.Gly38Arg (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a058), followed by p.Glu22Gly (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a011), p.Asn140His (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010), and the novel p.Leu120Val (\n                      <jats:italic>n<\/jats:italic>\n                      \u00a0=\u00a010). Most mutations were characterized by a protracted course, and some of them by atypical phenotypes. Older age of onset was independently associated with faster disease progression (exp[Estimate]\u00a0=\u00a01.03 [0.01, 0.05],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u20090.001) and poorer survival (hazard ratio\u00a01.05 [1.01, 1.08],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u20090.007), regardless of the underlying mutation. Female sex was independently associated with faster disease progression (exp[Estimate]\u00a0=\u00a02.1 [1.23, 3.65],\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u20090.012) in patients carrying the p.Gly38Arg mutation, resulting in shorter survival compared with male carriers (236 vs. 301\u2009months).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      These data may help to evaluate the efficacy of\n                      <jats:italic>SOD1<\/jats:italic>\n                      targeted treatments, and to expand the number of patients that might benefit from these treatments.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/ene.15661","type":"journal-article","created":{"date-parts":[[2022,12,9]],"date-time":"2022-12-09T09:29:48Z","timestamp":1670578188000},"page":"861-871","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Characterizing\n                    <scp>\n                      <i>SOD1<\/i>\n                    <\/scp>\n                    mutations in Spain: The impact of genotype, age and sex in the natural history of the disease"],"prefix":"10.1111","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3043-7938","authenticated-orcid":false,"given":"Juan F.","family":"V\u00e1zquez\u2010Costa","sequence":"first","affiliation":[{"name":"Neuromuscular Unit Hospital Universitario y Polit\u00e9cnico la Fe, IIS La Fe  Valencia Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)  Valencia Spain"},{"name":"Department of Medicine Universitat de Val\u00e8ncia  Valencia Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Borrego\u2010Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Neurology Department Hospital Universitario 12 de Octubre and Instituto de Investigaci\u00f3n Biom\u00e9dica Hospital 12 de Octubre  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Paradas","sequence":"additional","affiliation":[{"name":"Hospital Universitario Virgen del Roc\u00edo and Instituto Biomedicina de Sevilla  Sevilla Spain"},{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Neurodegenerativas (CIBERNED)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Teresa","family":"G\u00f3mez\u2010Caravaca","sequence":"additional","affiliation":[{"name":"Hospital Universitario Reina Sof\u00eda  C\u00f3rdoba Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Rojas\u2010Garcia","sequence":"additional","affiliation":[{"name":"Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras (CIBERER)  Valencia Spain"},{"name":"Motor Neuron Diseases Clinic, Department of Neurology, Biomedical Research Institute Sant Pau, Hospital de la Santa Creu i Sant Pau Universitat Aut\u00f2noma de Barcelona  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luis","family":"Varona","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital Universitario de Basurto  Bilbao Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M\u00f3nica","family":"Povedano","sequence":"additional","affiliation":[{"name":"Department of Neurology Hospital de Bellvitge and Idibell  Barcelona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8067-431X","authenticated-orcid":false,"given":"Tania","family":"Garc\u00eda\u2010Sobrino","sequence":"additional","affiliation":[{"name":"Department of Neurology Complejo Hospitalario Universitario de Santiago  Santiago de Compostela (A Coru\u00f1a) Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivonne","family":"Jeric\u00f3\u00a0Pascual","sequence":"additional","affiliation":[{"name":"Hospital Universitario de Navarra (HUN) and IdisNA  Pamplona Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Complejo Hospitalario Universitario Insular\u2010Materno\u2010Infantil de Gran Canaria  Gran Canaria Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7929-1055","authenticated-orcid":false,"given":"Javier","family":"Riancho","sequence":"additional","affiliation":[{"name":"Hospital Sierrallana\u2010IDIVAL. 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