{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T21:47:13Z","timestamp":1788385633331,"version":"build-2803163510"},"reference-count":45,"publisher":"BMJ","issue":"4","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2024,12,22]]},"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Considerable heterogeneity in genotypes and phenotypes has been observed among patients with amyotrophic lateral sclerosis (ALS) harbouring optineurin gene (\n                      <jats:italic>OPTN<\/jats:italic>\n                      ) mutations, as reported in prior studies. The study aimed to elucidate the correlation between\n                      <jats:italic>OPTN<\/jats:italic>\n                      genotypes and phenotypes.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      <jats:italic>OPTN<\/jats:italic>\n                      gene variants were screened within a substantial Chinese cohort of patients with ALS, encompassing LoF and rare missense variants. Additionally, a systematic literature review was conducted to compile the spectrum of\n                      <jats:italic>OPTN<\/jats:italic>\n                      mutations and explore the relationship between the genotype and phenotype of patients with ALS with\n                      <jats:italic>OPTN<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 33 unrelated patients with ALS with 24 rare\n                      <jats:italic>OPTN<\/jats:italic>\n                      variants, including 17 novel variants, were identified in 2279 patients with ALS. Among 24 variants in our cohort and 106 variants in previous studies, only 33.3% and 35.8% were pathogenic\/likely pathogenic variants. Moreover, the frequency of\n                      <jats:italic>OPTN<\/jats:italic>\n                      variants in the Asian ALS population was higher (1.08%) than that of the Caucasian population (0.55%). For the phenotype of patients with ALS carrying OPTN variants, we found that patients with pathogenic\/likely pathogenic variants had the highest baseline progression rate and the shortest survival time among groups in our cohort.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study contributed to a broader understanding of the genotype and phenotype spectrum of patients with ALS carrying\n                      <jats:italic>OPTN<\/jats:italic>\n                      variants. Further investigations are warranted to definitively establish the genotype-phenotype associations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2024-109978","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T13:20:25Z","timestamp":1736342425000},"page":"242-248","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Genetic and clinical analysis of\n                    <i>OPTN<\/i>\n                    in amyotrophic lateral sclerosis"],"prefix":"10.1136","volume":"62","author":[{"given":"Yi","family":"Xiao","sequence":"first","affiliation":[{"name":"Department of Neurology, West China Hospital, Sichuan University, Chengdu, Sichuan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yushan","family":"Tan","sequence":"additional","affiliation":[{"name":"Department of Neurology, West China Hospital, Sichuan University, Chengdu, 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