{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T04:21:57Z","timestamp":1792642917936,"version":"4.5.0"},"reference-count":18,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2017,3,22]],"date-time":"2017-03-22T00:00:00Z","timestamp":1490140800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Euro J of Neurology"],"published-print":{"date-parts":[[2017,5]]},"abstract":"<jats:sec><jats:title>Background and purpose<\/jats:title><jats:p>Hereditary spastic paraplegia is a clinically and genetically heterogeneous group of rare, inherited disorders causing an upper motor neuron syndrome with (complex) or without (pure) additional neurological symptoms. Mutations in the <jats:italic><jats:styled-content style=\"fixed-case\">KIF<\/jats:styled-content>1A<\/jats:italic> gene have already been associated with recessive and dominant forms of hereditary spastic paraplegia (<jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>30) in a few cases.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>All family members included in the study were examined neurologically. Whole\u2010exome sequencing was used in affected individuals to identify the responsible candidate gene. Conventional Sanger sequencing was conducted to validate familial segregation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A family of Macedonian origin with two affected siblings, one with slowly progressive and the other one with a more complex and rapidly progressing hereditary spastic paraplegia is reported. In both affected individuals, two novel pathogenic mutations outside the motor domain of the <jats:italic><jats:styled-content style=\"fixed-case\">KIF<\/jats:styled-content>1A<\/jats:italic> gene were found (<jats:styled-content style=\"fixed-case\">NM<\/jats:styled-content>_001244008.1:c.2909G&gt;A, p.Arg970His and c.1214dup, p.Asn405Lysfs*40) that segregate with the disease within the family establishing the diagnosis of autosomal recessive <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>30.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This report provides the first evidence that mutations outside the motor domain of the gene can cause (recessive) <jats:styled-content style=\"fixed-case\">SPG<\/jats:styled-content>30 and extends the genotype\u2212phenotype association for <jats:italic><jats:styled-content style=\"fixed-case\">KIF<\/jats:styled-content>1A<\/jats:italic>\u2010related diseases.<\/jats:p><\/jats:sec>","DOI":"10.1111\/ene.13279","type":"journal-article","created":{"date-parts":[[2017,3,24]],"date-time":"2017-03-24T01:45:06Z","timestamp":1490319906000},"page":"741-747","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Hereditary spastic paraplegia caused by compound heterozygous mutations outside the motor domain of the <i>KIF1A<\/i> gene"],"prefix":"10.1111","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3026-3082","authenticated-orcid":false,"given":"M.","family":"Krenn","sequence":"first","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Zulehner","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C.","family":"Hotzy","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Rath","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"E.","family":"Stogmann","sequence":"additional","affiliation":[{"name":"Department of Neurology Medical University of Vienna Vienna Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Wagner","sequence":"additional","affiliation":[{"name":"Institute of Human Genetics Technical University Munich Munich Germany"},{"name":"Institute of Neurogenomics Helmholtz Zentrum M\u00fcnchen Neuherberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"T. 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