{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T16:08:38Z","timestamp":1785600518253,"version":"3.56.0"},"reference-count":20,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T00:00:00Z","timestamp":1636416000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["BMC Neurol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                <jats:title>Background<\/jats:title>\n                <jats:p>Spastic paraplegia type 4 (SPG4) is caused by mutations in the <jats:italic>SPAST<\/jats:italic> gene, is the most common form of autosomal-dominant pure hereditary spastic paraplegias (HSP), and is rarely associated with a complicated form that includes ataxia, epilepsy, and cognitive decline. To date, the genotype-phenotype correlation has not been substantially established for <jats:italic>SPAST<\/jats:italic> mutations.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Case presentation<\/jats:title>\n                <jats:p>We present a Japanese patient with infantile-onset HSP and a complex form with coexisting ataxia and epilepsy. The sequencing of <jats:italic>SPAST<\/jats:italic> revealed a de novo c.1496G\u2009&gt;\u2009A (p.R499H) mutation. A review of the literature revealed 16 additional patients with p.R499H mutations in <jats:italic>SPAST<\/jats:italic> associated with an early-onset complicated form of HSP. We found that the complicated phenotype of patients with p.Arg499His mutations could be mainly divided into three subgroups: (1) infantile-onset ascending hereditary spastic paralysis, (2) HSP with severe dystonia, and (3) HSP with cognitive impairment. Moreover, the c.1496G\u2009&gt;\u2009A mutation in <jats:italic>SPAST<\/jats:italic> may occur as a de novo variant at noticeably high rates.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusion<\/jats:title>\n                <jats:p>We reviewed the clinical features of the patients reported in the literature with the p.Arg499His mutation in <jats:italic>SPAST<\/jats:italic> and described the case of a Japanese patient with this mutation presenting a new complicated form. Accumulating evidence suggests a possible association between infantile-onset complicated HSP and the p.Arg499His mutation in <jats:italic>SPAST.<\/jats:italic> The findings of this study may expand the clinical spectrum of the p.Arg499His mutation in <jats:italic>SPAST<\/jats:italic> and provide an opportunity to further study the genotype-phenotype correlation of SPG4.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s12883-021-02478-0","type":"journal-article","created":{"date-parts":[[2021,11,9]],"date-time":"2021-11-09T10:02:57Z","timestamp":1636452177000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["A p.Arg499His mutation in SPAST is associated with infantile-onset complicated spastic paraplegia: a case report and review of the literature"],"prefix":"10.1186","volume":"21","author":[{"given":"Haitian","family":"Nan","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroshi","family":"Shiraku","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Mizuno","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5400-7107","authenticated-orcid":false,"given":"Yoshihisa","family":"Takiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,11,9]]},"reference":[{"issue":"1","key":"2478_CR1","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1007\/s11910-996-0011-1","volume":"6","author":"JK Fink","year":"2006","unstructured":"Fink JK. 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Written informed consent was obtained from the parents of the patient.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"The parents of the patient gave written consent on behalf of the patient and the patient\u2019s sisters for their personal and clinical details along with any identifying images to be published in this study. The patient\u2019s father provided written informed consent for publication of this case report.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare that they have no conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"439"}}