{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:40:41Z","timestamp":1791214841228,"version":"4.1.0"},"reference-count":31,"publisher":"BMJ","issue":"2","content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["J Med Genet"],"accepted":{"date-parts":[[2013,11,2]]},"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Hereditary spastic paraparesis (HSP) (syn. Hereditary spastic paraplegia, SPG) are a group of genetic disorders characterised by spasticity of the lower limbs due to pyramidal tract dysfunction. Nearly 60 disease loci have been identified, which include mutations in two genes (\n                      <jats:italic>KIF5A<\/jats:italic>\n                      and\n                      <jats:italic>KIF1A<\/jats:italic>\n                      ) that encode motor proteins of the kinesin superfamily. Here we report a novel genetic defect in\n                      <jats:italic>KIF1C<\/jats:italic>\n                      of patients with spastic paraparesis and cerebellar dysfunction in two consanguineous families of Palestinian and Moroccan ancestry.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>\n                      We performed autozygosity mapping in a Palestinian and classic linkage analysis in a Moroccan family and found a locus on chromosome 17 that had previously been associated with spastic ataxia type 2 (SPAX2, OMIM %611302). Whole-exome sequencing revealed two homozygous mutations in\n                      <jats:italic>KIF1C<\/jats:italic>\n                      that were absent among controls: a nonsense mutation (c.2191C&gt;T, p.Arg731*) that segregated with the disease phenotype in the Palestinian kindred resulted in the entire absence of KIF1C protein from the patient's fibroblasts, and a missense variant (c.505C&gt;T, p.Arg169Trp) affecting a conserved amino acid of the motor domain that was found in the Moroccan kindred.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Kinesin genes encode a family of cargo\/motor proteins and are known to cause HSP if mutated. Here we identified nonsense and missense mutations in a further member of this protein family. The\n                      <jats:italic>KIF1C<\/jats:italic>\n                      mutation is associated with a HSP subtype (SPAX2\/SAX2) that combines spastic paraplegia and weakness with cerebellar dysfunction.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/jmedgenet-2013-102012","type":"journal-article","created":{"date-parts":[[2013,12,6]],"date-time":"2013-12-06T23:58:22Z","timestamp":1386374302000},"page":"137-142","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":85,"title":["<i>KIF1C<\/i>\n                    mutations in two families with hereditary spastic paraparesis and cerebellar dysfunction"],"prefix":"10.1136","volume":"51","author":[{"given":"Talya","family":"Dor","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Neuropediatric Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuval","family":"Cinnamon","sequence":"additional","affiliation":[{"name":"Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laure","family":"Raymond","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l'Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, UPMC Univ Paris VI UMR_S975; CNRS UMR 7225; INSERM U975, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"},{"name":"Groupe de Neurog\u00e9n\u00e9tique, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avraham","family":"Shaag","sequence":"additional","affiliation":[{"name":"Department of Genetic Research, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naima","family":"Bouslam","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l'Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, UPMC Univ Paris VI UMR_S975; CNRS UMR 7225; INSERM U975, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"},{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V Souissi, Equipe de recherche des maladies neurod\u00e9g\u00e9neratives (ERMN), Rabat, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Bouhouche","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V Souissi, Equipe de recherche des maladies neurod\u00e9g\u00e9neratives (ERMN), Rabat, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marion","family":"Gaussen","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l'Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, UPMC Univ Paris VI UMR_S975; CNRS UMR 7225; INSERM U975, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"},{"name":"Groupe de Neurog\u00e9n\u00e9tique, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vincent","family":"Meyer","sequence":"additional","affiliation":[{"name":"Genoscope, Evry, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Durr","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l'Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, UPMC Univ Paris VI UMR_S975; CNRS UMR 7225; INSERM U975, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"},{"name":"APHP, F\u00e9d\u00e9ration de G\u00e9n\u00e9tique, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexis","family":"Brice","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l'Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, UPMC Univ Paris VI UMR_S975; CNRS UMR 7225; INSERM U975, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"},{"name":"APHP, F\u00e9d\u00e9ration de G\u00e9n\u00e9tique, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ali","family":"Benomar","sequence":"additional","affiliation":[{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V Souissi, Equipe de recherche des maladies neurod\u00e9g\u00e9neratives (ERMN), Rabat, Morocco"},{"name":"Facult\u00e9 de M\u00e9decine et de Pharmacie de Rabat, Universit\u00e9 Mohammed V Souissi, Centre de recherche en \u00e9pid\u00e9miologie clinique et essai th\u00e9rapeutique (CRECET), Rabat, Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giovanni","family":"Stevanin","sequence":"additional","affiliation":[{"name":"Centre de Recherche de l'Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, UPMC Univ Paris VI UMR_S975; CNRS UMR 7225; INSERM U975, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"},{"name":"Groupe de Neurog\u00e9n\u00e9tique, Ecole Pratique des Hautes Etudes, Institut du Cerveau et de la Moelle \u00e9pini\u00e8re, Paris, France"},{"name":"APHP, F\u00e9d\u00e9ration de G\u00e9n\u00e9tique, H\u00f4pital de la Piti\u00e9-Salp\u00eatri\u00e8re, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Schuelke","sequence":"additional","affiliation":[{"name":"Department of Neuropediatrics and NeuroCure Clinical Research Center, Charit\u00e9 Universit\u00e4tsmedizin Berlin, Augustenburger Platz 1, Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Edvardson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Neuropediatric Unit, Hadassah-Hebrew University Medical Center, Jerusalem, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"239","published-online":{"date-parts":[[2013,12,6]]},"reference":[{"key":"2025101710015220000_51.2.137.1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02224539"},{"key":"2025101710015220000_51.2.137.2","first-page":"512","article-title":"\u00dcber famili\u00e4re Formen von cerebralen Diplegien","volume":"12","author":"Freud","year":"1893","journal-title":"Neurol Zentralblatt"},{"key":"2025101710015220000_51.2.137.3","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.1016\/S0140-6736(83)92879-9","article-title":"Classification of the hereditary ataxias and paraplegias","volume":"321","author":"Harding","year":"1983","journal-title":"The Lancet"},{"key":"2025101710015220000_51.2.137.4","unstructured":"Fink JK . Hereditary Spastic Paraplegia Overview. In: Pagon RA Adam MP Bird TD Dolan CR Fong C-T Stephens K . eds GeneReviewsTM . Seattle, WA: University of Washington, 1993. http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1509\/ (accessed 15 Oct 2013)."},{"key":"2025101710015220000_51.2.137.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2012.03.025"},{"key":"2025101710015220000_51.2.137.6","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-neuro-062111-150400"},{"key":"2025101710015220000_51.2.137.7","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1055\/s-0031-1299787","article-title":"Genetics of hereditary spastic paraplegias","volume":"31","author":"Sch\u00fcle","year":"2012","journal-title":"Semin Neurol"},{"key":"2025101710015220000_51.2.137.8","doi-asserted-by":"publisher","DOI":"10.1038\/emboj.2010.51"},{"key":"2025101710015220000_51.2.137.9","doi-asserted-by":"publisher","DOI":"10.1086\/344210"},{"key":"2025101710015220000_51.2.137.10","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2011.03.009"},{"key":"2025101710015220000_51.2.137.11","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2662"},{"key":"2025101710015220000_51.2.137.12","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddp324"},{"key":"2025101710015220000_51.2.137.13","doi-asserted-by":"publisher","DOI":"10.1101\/gr.117143.110"},{"key":"2025101710015220000_51.2.137.14","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.2011.01717.x"},{"key":"2025101710015220000_51.2.137.15","doi-asserted-by":"publisher","DOI":"10.1002\/humu.20920"},{"key":"2025101710015220000_51.2.137.16","doi-asserted-by":"publisher","DOI":"10.1086\/521227"},{"key":"2025101710015220000_51.2.137.17","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks487"},{"key":"2025101710015220000_51.2.137.18","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-010-0249-2"},{"key":"2025101710015220000_51.2.137.19","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts199"},{"key":"2025101710015220000_51.2.137.20","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btp698"},{"key":"2025101710015220000_51.2.137.21","doi-asserted-by":"publisher","DOI":"10.1038\/ng.806"},{"key":"2025101710015220000_51.2.137.22","doi-asserted-by":"publisher","DOI":"10.1101\/gr.107524.110"},{"key":"2025101710015220000_51.2.137.23","doi-asserted-by":"publisher","DOI":"10.1038\/nmeth0810-575"},{"key":"2025101710015220000_51.2.137.24","doi-asserted-by":"publisher","DOI":"10.1038\/nature11632"},{"key":"2025101710015220000_51.2.137.25","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-007-0328-0"},{"key":"2025101710015220000_51.2.137.26","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2011.261"},{"key":"2025101710015220000_51.2.137.27","doi-asserted-by":"publisher","DOI":"10.1128\/MCB.22.3.866-873.2002"},{"key":"2025101710015220000_51.2.137.28","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2012.11.005"},{"key":"2025101710015220000_51.2.137.29","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.12.012"},{"key":"2025101710015220000_51.2.137.30","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.11.021"},{"key":"2025101710015220000_51.2.137.31","unstructured":"Campbell WW DeJong RN Haerer AF . DeJongs's the neurologic examination. 6th edn. 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