{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T13:39:03Z","timestamp":1762522743584,"version":"3.41.2"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,7,14]],"date-time":"2022-07-14T00:00:00Z","timestamp":1657756800000},"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>Hereditary Spastic Paraplegia (HSP) is considered to be one of the common neurodegenerative diseases with marked genetic heterogeneity. Recently, the mutations in ubiquitin-associated protein 1 (<jats:italic>UBAP1<\/jats:italic>) have been described in patients with HSP, known as spastic paraplegias 80 (SPG80). Here, we reported a Chinese HSP family presenting a frameshift mutation in the <jats:italic>UBAP1<\/jats:italic> gene leading to complex HSP. Their clinical features encompassed spastic paraparetic gait, exaggerated patellar tendon reflexes, bilateral Babinski signs, and hyperactive Achilles tendon reflex. The proband also had severe urinary incontinence and a dermoid cyst at the lumbar 4\u20135 spinal cord, which rarely occurs in HSP patients. Following whole-exome sequencing, a novel heterozygous mutation (c.437dupG, NM_016,525) was identified in the <jats:italic>UBAP1<\/jats:italic> that segregated with the family\u2019s phenotype and resulted in truncating UBAP1 protein (p.Ser146ArgfsTer13). Moreover, we reviewed the genotypes of <jats:italic>UBAP1<\/jats:italic> and the phenotypic variability in 90 HSP patients reported in the literature. We found that the age of onset in UBAP1-related patients was juvenile, and there were population differences in the age of onset. The main complications were lower extremity spasticity, hyperreflexia, and the Babinski sign. Exon 4 of UBAP1 was identified as a mutation hotspot region. Our study expands the knowledge of UBAP1 mutations, which will aid in HSP patient counseling. Further molecular biological research is needed to explore the genotype-phenotype correlations of UBAP1-related HSP.<\/jats:p>","DOI":"10.3389\/fgene.2022.936292","type":"journal-article","created":{"date-parts":[[2022,7,19]],"date-time":"2022-07-19T08:21:19Z","timestamp":1658218879000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["A novel mutation in the UBAP1 gene causing hereditary spastic paraplegia: A case report and overview of the genotype-phenotype correlation"],"prefix":"10.3389","volume":"13","author":[{"given":"Peiqiang","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiande","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Senmao","family":"Chai","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dalin","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Huirong","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengdie","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shasha","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaodong","family":"Xie","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,7,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1016\/j.str.2011.12.013","article-title":"The UBAP1 subunit of ESCRT-I interacts with ubiquitin via a SOUBA domain","volume":"20","author":"Agromayor","year":"2012","journal-title":"Structure"},{"key":"B2","doi-asserted-by":"publisher","first-page":"e0253871","DOI":"10.1371\/journal.pone.0253871","article-title":"Two novel truncating variants in UBAP1 are responsible for hereditary spastic paraplegia","volume":"16","author":"Bian","year":"2021","journal-title":"PLoS One"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1763","DOI":"10.1038\/s41431-020-00720-w","article-title":"Identification of UBAP1 mutations in juvenile hereditary spastic paraplegia in the 100,000 Genomes Project","volume":"28","author":"Bourinaris","year":"2020","journal-title":"Eur. 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