{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,25]],"date-time":"2026-07-25T21:15:29Z","timestamp":1785014129782,"version":"3.55.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T00:00:00Z","timestamp":1767830400000},"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. Med."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Variants in the\n                      <jats:italic>KIF1A<\/jats:italic>\n                      have been associated with a wide range of phenotypes. Most variants are found in the protein\u2019s motor domain. The clinical phenotype of\n                      <jats:italic>KIF1A<\/jats:italic>\n                      -associated disorders (KAND) correlates with the position and the type of variant. Missense variants in the motor domain are predominantly associated with severe phenotypes and often occur\n                      <jats:italic>de novo<\/jats:italic>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Patients from the Czech Republic and Switzerland were identified during DNA diagnostics for neuromuscular or neurodevelopmental disorders. Clinical and genetic data were analyzed retrospectively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 18 patients with heterozygous\n                      <jats:italic>KIF1A<\/jats:italic>\n                      variants were reported. The clinical spectrum ranges from a very severe congenital phenotype to mild spastic paraplegia or early-onset slowly progressive neuropathy. Among patients with early clinical manifestation (n\u202f=\u202f13; congenital symptoms, gross motor delay, complicated\/pure spastic paraplegia, neuropathy), all detected variants were missense and localized in the motor domain, eight times confirmed to be\n                      <jats:italic>de novo<\/jats:italic>\n                      . In individuals with adult onset (\n                      <jats:italic>n<\/jats:italic>\n                      \u202f=\u202f5; all spastic paraplegia), a frameshift variant outside the motor domain was also detected in one case.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      KAND phenotypes are not only limited to severe and early-onset phenotypes but also include adult-onset less severe ones. The localization of a missense\n                      <jats:italic>KIF1A<\/jats:italic>\n                      variant in the motor domain corresponds with a more severe disease, but not exclusively. Given the broad phenotypic spectrum associated with\n                      <jats:italic>KIF1A<\/jats:italic>\n                      variants, each variant should be individually evaluated for pathogenicity. Based on our findings, we propose a supporting algorithm outlining key considerations to support variant causality and the prediction of the associated phenotype.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmed.2025.1704209","type":"journal-article","created":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T06:36:23Z","timestamp":1767854183000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Genotype\u2013phenotype correlations in 18 European patients with heterozygous KIF1A variants: key considerations for assessing KIF1A variant causality"],"prefix":"10.3389","volume":"12","author":[{"given":"Anna","family":"Uhrova 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