{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T17:42:17Z","timestamp":1760722937826,"version":"build-2065373602"},"reference-count":23,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T00:00:00Z","timestamp":1750809600000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2025,6,8]]},"published-print":{"date-parts":[[2025,10]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Variants in the Kinesin-family member 5A (\n                      <jats:italic>KIF5A)<\/jats:italic>\n                      gene are associated with a range of motor diseases, and a strong correlation between the protein domains (motor, stalk and tail) and the clinical phenotype has been proposed. However, several studies have reported exceptions contributing to a complex genotype\u2013phenotype correlation in recent years. Further studies are needed to improve our knowledge about the prevalence of\n                      <jats:italic>KIF5A<\/jats:italic>\n                      variants and their genotype\u2013phenotype correlation.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>390 patients (220 hereditary spastic paraplegia, 80 Charcot-Marie-Tooth disease type 2 and 90 amyotrophic lateral sclerosis) have been selected for next-generation sequencing Clinical Exome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Five patients have been found to carry causative variants in the\n                      <jats:italic>KIF5A<\/jats:italic>\n                      gene. Of these, three are familiar cases, and two are sporadic. Segregation analysis was performed on the familiar probands. The five patients with pathogenic variants represent 4% of the studied population, and the clinical and genetic analysis of these five families allowed us to examine different scenarios.\n                    <\/jats:p>\n                    <jats:p>Some of these data support the hypothesis of a complex correlation between domains and disease.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These data confirm the complex genotype\u2013phenotype correlation, both in terms of clinical heterogeneity associated with a specific domain and variability within the members of the same family, but also suggest a strong genotype\u2013phenotype correlation, both intrafamiliar and interfamiliar, produced by a few variants.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmg-2025-110801","type":"journal-article","created":{"date-parts":[[2025,6,25]],"date-time":"2025-06-25T13:20:23Z","timestamp":1750857623000},"page":"641-646","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["New variants and genotype\u2013phenotype correlation in\n                    <i>KIF5A<\/i>\n                    mutation: the contribution of a large Italian cohort"],"prefix":"10.1136","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8899-0309","authenticated-orcid":false,"given":"Rosangela","family":"Ferese","sequence":"first","affiliation":[{"name":"IRCCS Neuromed, Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Suppa","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Pozzilli, Italy"},{"name":"Department of Human Neurosciences, University of Rome La Sapienza, Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosa","family":"Campopiano","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona","family":"Scala","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Federica","family":"Sammarone","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luana","family":"Di Pilla","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alba","family":"Di Pardo","sequence":"additional","affiliation":[{"name":"IRCCS Neuromed, Pozzilli, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria 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