{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T16:33:16Z","timestamp":1778689996959,"version":"3.51.4"},"reference-count":19,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2014,12,2]],"date-time":"2014-12-02T00:00:00Z","timestamp":1417478400000},"content-version":"unspecified","delay-in-days":1006,"URL":"https:\/\/www.cambridge.org\/core\/terms"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Can. J. Neurol. Sci."],"published-print":{"date-parts":[[2012,3]]},"abstract":"<jats:sec id=\"S0317167100013263_abs1\"><jats:title>Objectives:<\/jats:title><jats:p>To characterize at clinical and molecular levels a family presenting with X-linked recessive Hereditary Spastic Paraplegia (HSP).<\/jats:p><\/jats:sec><jats:sec id=\"S0317167100013263_abs2\"><jats:title>Background:<\/jats:title><jats:p>HSPs are a large group of genetically heterogeneous neurodegenerative disorders characterized by progressive upper motor neuron signs. Mutations in the proteolipid protein <jats:italic>(PLP1)<\/jats:italic> gene have been identified in families linked to the SPG2 locus on chromosome Xq22. However, Pelizaeus-Merzbacher disease (PMD) is also an X-linked recessive neurological disorder caused by <jats:italic>PLP1<\/jats:italic> mutations.<\/jats:p><\/jats:sec><jats:sec id=\"S0317167100013263_abs3\"><jats:title>Methods:<\/jats:title><jats:p>The SPG2 locus was investigated by linkage analysis in the family. The <jats:italic>PLP1<\/jats:italic> gene was screened by sequencing. We present findings in a large French-Canadian family with an X-linked recessive HSP. The proband presented early with developmental delay and developed progressive spastic paraplegia. He has been wheelchair-bound since the age of three years. At the latest follow-up, he was 20 years-old and had severe spasticity predominantly affecting the lower extremities, moderate cerebellar dysfunction, and optic atrophy.<\/jats:p><\/jats:sec><jats:sec id=\"S0317167100013263_abs4\"><jats:title>Results:<\/jats:title><jats:p>Linkage to SPG2 was established and a G to A mutation (M1R) in the initiation codon of the <jats:italic>PLP1<\/jats:italic> gene was identified, likely resulting in the complete absence of proteolipid protein.<\/jats:p><\/jats:sec><jats:sec id=\"S0317167100013263_abs5\"><jats:title>Conclusion:<\/jats:title><jats:p>We report a new <jats:italic>PLP1<\/jats:italic> gene mutation in a patient with a clinical phenotype consistent with a PLP1 null syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1017\/s0317167100013263","type":"journal-article","created":{"date-parts":[[2014,12,12]],"date-time":"2014-12-12T15:03:35Z","timestamp":1418396615000},"page":"220-224","source":"Crossref","is-referenced-by-count":6,"title":["A Novel <i>PLP1<\/i> Mutation Further Expands the Clinical Heterogeneity at the Locus"],"prefix":"10.1017","volume":"39","author":[{"given":"Collette Kathleen","family":"Hand","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genevi\u00e8ve","family":"Bernard","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marie-Pierre","family":"Dub\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael Israel","family":"Shevell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy Armand","family":"Rouleau","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"56","published-online":{"date-parts":[[2014,12,2]]},"reference":[{"key":"S0317167100013263_ref015","doi-asserted-by":"publisher","DOI":"10.1159\/000111361"},{"key":"S0317167100013263_ref017","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.30.5.381"},{"key":"S0317167100013263_ref005","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-008-0130-8"},{"key":"S0317167100013263_ref016","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.84.16.5665"},{"key":"S0317167100013263_ref014","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200537"},{"key":"S0317167100013263_ref009","doi-asserted-by":"publisher","DOI":"10.1007\/BF02185767"},{"key":"S0317167100013263_ref007","doi-asserted-by":"publisher","DOI":"10.1007\/s10048-004-0207-y"},{"key":"S0317167100013263_ref003","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1007\/s004390050507","article-title":"Evidence of a third locus in X-linked recessive spastic paraplegia","volume":"100","author":"Steinm\u00fcller","year":"1997","journal-title":"Hum Genet"},{"key":"S0317167100013263_ref013","doi-asserted-by":"publisher","DOI":"10.1177\/088307388600100310"},{"key":"S0317167100013263_ref001","doi-asserted-by":"publisher","DOI":"10.1038\/ng0794-402"},{"key":"S0317167100013263_ref004","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(20000904)94:1<5::AID-AJMG2>3.0.CO;2-O"},{"key":"S0317167100013263_ref011","first-page":"1355","article-title":"Complete deletion of the proteolipid protein gene (PLP) in a family with X-linked Pelizaeus-Merzbacher disease","volume":"49","author":"Raskind","year":"1991","journal-title":"Am J Hum Genet"},{"key":"S0317167100013263_ref006","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.86.20.8128"},{"key":"S0317167100013263_ref010","first-page":"360","article-title":"Proteolipoprotein gene analysis in 82 patients with sporadic Pelizaeus-Merzbacher Disease: duplications, the major cause of the disease, originate more frequently in male germ cells, but point mutations do not","volume":"65","author":"Mimault","year":"1999","journal-title":"The Clinical European Network on Brain Dysmyelinating Disease. Am J Hum Genet"},{"key":"S0317167100013263_ref012","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.50.6.1749"},{"key":"S0317167100013263_ref018","doi-asserted-by":"publisher","DOI":"10.1016\/S0896-6273(00)80360-8"},{"key":"S0317167100013263_ref002","doi-asserted-by":"publisher","DOI":"10.1038\/ng0394-257"},{"key":"S0317167100013263_ref008","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(199905)45:5<624::AID-ANA11>3.0.CO;2-1"},{"key":"S0317167100013263_ref019","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf043"}],"container-title":["Canadian Journal of Neurological Sciences \/ Journal Canadien des Sciences Neurologiques"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.cambridge.org\/core\/services\/aop-cambridge-core\/content\/view\/S0317167100013263","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,4,11]],"date-time":"2019-04-11T16:13:28Z","timestamp":1554999208000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.cambridge.org\/core\/product\/identifier\/S0317167100013263\/type\/journal_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,3]]},"references-count":19,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2012,3]]}},"alternative-id":["S0317167100013263"],"URL":"https:\/\/doi.org\/10.1017\/s0317167100013263","relation":{},"ISSN":["0317-1671","2057-0155"],"issn-type":[{"value":"0317-1671","type":"print"},{"value":"2057-0155","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,3]]}}}