{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,12]],"date-time":"2026-02-12T18:04:56Z","timestamp":1770919496255,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T00:00:00Z","timestamp":1698710400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Hereditary spastic paraplegia (HSP) is a progressive upper-motor neurodegenerative disease. Mutations in the <jats:italic>WASHC5<\/jats:italic> gene are associated with autosomal dominant HSP, spastic paraplegia 8 (SPG8). However, due to the small number of reported cases, the exact mechanism remains unclear.<\/jats:p><jats:p><jats:bold>Method:<\/jats:bold> We report a Chinese family with HSP. The proband was referred to our hospital due to restless leg syndrome and insomnia. The preliminary clinical diagnosis of the proband was spastic paraplegia. Whole-exome sequencing (WES) and RNA splicing analysis were conducted to evaluate the genetic cause of the disease in this family.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A novel splice-altering variant (c.712\u20132A&amp;gt;G) in the <jats:italic>WASHC5<\/jats:italic> gene was detected and further verified by RNA splicing analysis and Sanger sequencing. Real-time qPCR analysis showed that the expression of genes involved in the Wiskott\u2013Aldrich syndrome protein and SCAR homolog (WASH) complex and endosomal and lysosomal systems was altered due to this variant.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> A novel heterozygous splice-altering variant (c.712\u20132A&amp;gt;G) in the <jats:italic>WASHC5<\/jats:italic> gene was detected in a Chinese family with HSP. Our study provided data for genetic counseling to this family and offered evidence that this splicing variant in the <jats:italic>WASHC5<\/jats:italic> gene is significant in causing HSP.<\/jats:p>","DOI":"10.3389\/fgene.2023.1205052","type":"journal-article","created":{"date-parts":[[2023,10,31]],"date-time":"2023-10-31T11:33:03Z","timestamp":1698751983000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Case report: A novel WASHC5 variant altering mRNA splicing causes spastic paraplegia in a patient"],"prefix":"10.3389","volume":"14","author":[{"given":"Shan-Yu","family":"Gao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu-Xing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Dong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liang-Liang","family":"Fan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qi","family":"Ding","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lv","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,10,31]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1002\/ajmg.a.61487","article-title":"Novel KIAA1033\/WASHC4 mutations in three patients with syndromic intellectual disability and a review of the literature","volume":"182","author":"Assoum","year":"2020","journal-title":"Am. 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