{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,3]],"date-time":"2026-05-03T10:30:18Z","timestamp":1777804218090,"version":"3.51.4"},"reference-count":15,"publisher":"SAGE Publications","issue":"5","license":[{"start":{"date-parts":[[2018,2,8]],"date-time":"2018-02-08T00:00:00Z","timestamp":1518048000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["J Child Neurol"],"published-print":{"date-parts":[[2018,4]]},"abstract":"<jats:p>Hereditary spastic paraplegia is a phenotypically and genetically heterogeneous group of neurodegenerative disorders characterized by lower extremity weakness and spasticity. Spastic paraplegia 4 (SPG4), caused by heterozygous mutations in the gene SPAST, typically causes a late-onset, uncomplicated form of hereditary spastic paraplegia in affected individuals. Additional clinical features in SPG4 have been reported on occasion, but no genotype-phenotype correlation has been established. Through targeted clinical testing, we identified 2 unrelated female patients with the same de novo p.Arg499His mutation in SPAST. Both patients presented with early-onset spasticity resulting in delayed motor milestones, which led to a diagnosis of cerebral palsy in one child and tethered cord in the other. Review of the literature identified several patients with mutations at amino acid 499 and early-onset symptoms associated with a risk of cognitive impairment. Early and accurate diagnosis of children with early-onset spasticity is important for informed prognosis and genetic counselling.<\/jats:p>","DOI":"10.1177\/0883073818756680","type":"journal-article","created":{"date-parts":[[2018,2,9]],"date-time":"2018-02-09T02:18:27Z","timestamp":1518142707000},"page":"329-332","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":16,"title":["Association of Early-Onset Spasticity and Risk for Cognitive Impairment With Mutations at Amino Acid 499 in\n                    <i>SPAST<\/i>"],"prefix":"10.1177","volume":"33","author":[{"given":"Meredith K.","family":"Gillespie","sequence":"first","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Humphreys","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada"},{"name":"Division of Neurology, Department of Pediatrics, Children\u2019s Hospital of Eastern Ontario, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hugh J.","family":"McMillan","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada"},{"name":"Division of Neurology, Department of Pediatrics, Children\u2019s Hospital of Eastern Ontario, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kym M.","family":"Boycott","sequence":"additional","affiliation":[{"name":"Children\u2019s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada"},{"name":"Department of Genetics, Children\u2019s Hospital of Eastern Ontario, Ottawa, ON, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2018,2,8]]},"reference":[{"key":"bibr1-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(83)92879-9"},{"key":"bibr2-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1055\/s-0034-1386767"},{"key":"bibr3-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1038\/15472"},{"key":"bibr4-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.2.153"},{"key":"bibr5-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10212"},{"key":"bibr6-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1038\/ejhg.2008.147"},{"key":"bibr7-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1212\/NXG.0000000000000122"},{"key":"bibr8-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.4.637"},{"key":"bibr9-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2009.09.025"},{"key":"bibr10-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2005.03.040"},{"key":"bibr11-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5201922"},{"key":"bibr12-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.62.7.1118"},{"key":"bibr13-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-016-8179-z"},{"key":"bibr14-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2005.035311"},{"key":"bibr15-0883073818756680","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-004-0186-z"}],"container-title":["Journal of Child Neurology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0883073818756680","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1177\/0883073818756680","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1177\/0883073818756680","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T20:39:23Z","timestamp":1777495163000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1177\/0883073818756680"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,2,8]]},"references-count":15,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2018,4]]}},"alternative-id":["10.1177\/0883073818756680"],"URL":"https:\/\/doi.org\/10.1177\/0883073818756680","relation":{},"ISSN":["0883-0738","1708-8283"],"issn-type":[{"value":"0883-0738","type":"print"},{"value":"1708-8283","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,2,8]]}}}