{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T03:16:25Z","timestamp":1783048585673,"version":"3.54.6"},"reference-count":16,"publisher":"Instituto Nacional de Salud (Colombia)","issue":"2","license":[{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"unspecified","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["revistabiomedica.org"],"crossmark-restriction":false},"short-container-title":["Biomed."],"abstract":"<jats:p>Hereditary spastic paraplegias are genetic disorders characterized by spasticity in the lower limbs, weakness, and sensory disturbances. Global prevalence ranges from 1.27 to 9.6 per 100 000 individuals. Mutations in the PLP1 gene cause various X-linked hereditary spastic paraplegias phenotypes, including Pelizaeus-Merzbacher disease and spastic paraplegia type 2.A 53-year-old male presented with chronic lower limb weakness since childhood, requiring a wheelchair at age 47 and exhibiting zero strength in the lower limbs. Magnetic resonance imaging revealed periventricular leukodystrophy; similar symptoms were found in maternal uncles and a nephew. The 32-year-old nephew had gait difficulties. A genetic sequencing panel identified a hemizygous variant of uncertain significance in the PLP1 gene [c.197A&gt;T (p.His66Leu)] in both, not reported in population genetic databases.X-linked spastic paraplegia 2 is a disease primarily affecting gait and causing lower limb weakness. Reports indicate that it may also include cognitive impairment, nystagmus, and ataxia, although in the studied family, weakness predominated without cerebellar symptoms. Thirty-six families with this condition have been documented worldwide, with cases of asymptomatic carrier females. The c.197A&gt;T (p.His66Leu) variant in the PLP1 gene, identified in this case, is novel and, despite being classified as \u201cof uncertain significance\u201d, could be pathogenic according to bioinformatic predictors, explaining the spastic paraplegia 2 presentation in this family.<\/jats:p>","DOI":"10.7705\/biomedica.7733","type":"journal-article","created":{"date-parts":[[2026,6,24]],"date-time":"2026-06-24T17:11:52Z","timestamp":1782321112000},"page":"203-210","update-policy":"https:\/\/doi.org\/10.7705\/crossmark","source":"Crossref","is-referenced-by-count":0,"title":["New variant in PLP1 gene associated with X-linked spastic paraplegia type 2: First report of a family in Colombia","Nueva variante del gen PLP1 asociada a paraplejia esp\u00e1stica de tipo 2, ligada a X: primer reporte de una familia en Colombia"],"prefix":"10.7705","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9756-0834","authenticated-orcid":false,"given":"Nicol\u00e1s","family":"Laverde-Sudupe","sequence":"first","affiliation":[{"name":"Facultad de Ciencias de la Salud, Departamento de Medicina, Pontificia Universidad Javeriana, Cali, Colombia"},{"name":"Facultad de Ciencias de la Salud"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3310-8718","authenticated-orcid":false,"given":"\u00c1ngela Lizeth","family":"Giraldo-Serna","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Salud, Departamento de Medicina, Pontificia Universidad Javeriana, Cali, Colombia"},{"name":"Facultad de Ciencias de la Salud, Departamento de Medicina, Pontificia Universidad Javeriana, Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9424-7554","authenticated-orcid":false,"given":"Diana","family":"Ram\u00edrez-Monta\u00f1o","sequence":"additional","affiliation":[{"name":"Departamento de Morfolog\u00eda, Escuela de Ciencias B\u00e1sicas, Facultad de Salud, Universidad del Valle, Cali, Colombia; Unidad de Medicina Gen\u00f3mica y Gen\u00e9tica, Cl\u00ednica Imbanaco, Cali, Colombia"},{"name":"Departamento de Morfolog\u00eda, Escuela de Ciencias B\u00e1sicas, Facultad de Salud, Universidad del Valle, Cali, Colombia; Unidad de Medicina Gen\u00f3mica y Gen\u00e9tica, Cl\u00ednica Imbanaco, Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5418-7710","authenticated-orcid":false,"given":"Juli\u00e1n","family":"Ram\u00edrez-Cheyne","sequence":"additional","affiliation":[{"name":"Departamento de Morfolog\u00eda, Escuela de Ciencias B\u00e1sicas, Facultad de Salud, Universidad del Valle, Cali, Colombia"},{"name":"Departamento de Morfolog\u00eda, Escuela de Ciencias B\u00e1sicas, Facultad de Salud, Universidad del Valle, Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7815-4390","authenticated-orcid":false,"given":"Wilmar","family":"Saldarriaga-Gil","sequence":"additional","affiliation":[{"name":"Departamento de Morfolog\u00eda, Escuela de Ciencias B\u00e1sicas, Facultad de Salud, Universidad del Valle, Cali, Colombia"},{"name":"Departamento de Morfolog\u00eda, Escuela de Ciencias B\u00e1sicas, Facultad de Salud, Universidad del Valle, Cali, Colombia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"4444","published-online":{"date-parts":[[2026,6,1]]},"reference":[{"key":"164322","doi-asserted-by":"crossref","unstructured":"Fink JK. The hereditary spastic paraplegias. Handb Clin Neurol. 2023;196:59-88. https:\/\/doi.org\/10.1016\/B978-0-323-98817-9.00022-3","DOI":"10.1016\/B978-0-323-98817-9.00022-3"},{"key":"164323","unstructured":"Hedera P. Hereditary spastic paraplegia overview. In: Adam MP, Feldman J, Mirzaa GM, et al., editors. GeneReviews\u00ae. Seattle, WA: University of Washington. Accessed: February 11, 2025. Available from: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1509\/"},{"key":"164324","unstructured":"Johns Hopkins University. OMIM\u2122. An online catalog of human genes and genetic disorders. Baltimore, MD: Johns Hopkins University. MIM number: 312920, Spastic Paraplegia 2, X-linked; SPG2. Accessed: March 14, 2024. Available from: https:\/\/omim.org\/"},{"key":"164325","doi-asserted-by":"crossref","unstructured":"Kim D, An H, Fan C, Park Y. Identifying oligodendrocyte enhancers governing Plp1 expression. Hum Mol Genet. 2021;30:2225-39. https:\/\/doi.org\/10.1093\/hmg\/ddab184","DOI":"10.1093\/hmg\/ddab184"},{"key":"164326","doi-asserted-by":"crossref","unstructured":"Yao L, Zhu Z, Zhang C, Tian W, Cao L. PLP1 gene mutations cause spastic paraplegia type 2 in three families. Ann Clin Transl Neurol. 2023;10:328-38. https:\/\/doi.org\/10.1002\/acn3.51722","DOI":"10.1002\/acn3.51722"},{"key":"164327","doi-asserted-by":"crossref","unstructured":"Cruzeiro MM, Vale TC, Marrone CD. Symptomatic female carriers of mutations in the Duchenne muscular dystrophy gene. Arq Neuropsiquiatr. 2020;78:598-9. https:\/\/doi.org\/10.1590\/0004-282X20200061","DOI":"10.1590\/0004-282x20200061"},{"key":"164328","doi-asserted-by":"crossref","unstructured":"Shen MC, Chang SP, Lee DJ, Lin WH, Chen M, Ma GC. Skewed X-chromosome inactivation and parental gonadal mosaicism are implicated in X-linked recessive female hemophilia patients. Diagnostics (Basel). 2022;12:2267. https:\/\/doi.org\/10.3390\/diagnostics12102267","DOI":"10.3390\/diagnostics12102267"},{"key":"164329","doi-asserted-by":"crossref","unstructured":"Yamamoto-Shimojima K, Imaizumi T, Aoki Y, Inoue K, Kaname T, Okuno Y, et al. Elucidation of the pathogenic mechanism and potential treatment strategy for a female patient with spastic paraplegia derived from a single-nucleotide deletion in PLP1. J Hum Genet. 2019;64:665-71. https:\/\/doi.org\/10.1038\/s10038-019-0600-x","DOI":"10.1038\/s10038-019-0600-x"},{"key":"164330","doi-asserted-by":"crossref","unstructured":"Kubota K, Saito Y, Ohba C, Saitsu H, Fukuyama T, Ishiyama A, et al. Brain magnetic resonance imaging findings and auditory brainstem response in a child with spastic paraplegia 2 due to a PLP1 splice site mutation. 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