{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,22]],"date-time":"2026-01-22T02:37:26Z","timestamp":1769049446670,"version":"3.49.0"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T00:00:00Z","timestamp":1649376000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p><jats:bold>Background:<\/jats:bold> Mutations in the <jats:italic>NIPA1<\/jats:italic> gene cause hereditary spastic paraplegia (HSP) type 6 (SPG6), which is a rare type of HSP with a frequency of less than 1% in Europe. To date, less than 30 SPG6 families and limited <jats:italic>NIPA1<\/jats:italic> mutations have been reported in different ethnic regions. The clinical features are variable.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> We screened for <jats:italic>NIPA1<\/jats:italic> mutations by whole exome sequencing or next generation sequencing in 35 unrelated Chinese families with HSP. The clinical manifestations were evaluated.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Two variants of <jats:italic>NIPA1<\/jats:italic> were identified in three index patients (3\/35, 8.6%), two of whom carried a previously reported common variant c.316G &amp;gt; A (p.G106R), and the third patient harbored a novel likely pathogenic variant c.126C &amp;gt; G (p.N42K). Both variants were <jats:italic>de novo<\/jats:italic> in the three index patients. The phenotype was pure HSP in two patients and complicated HSP with epilepsy in the third one.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold><jats:italic>NIPA1<\/jats:italic>-related HSP is more common in China than it in Europe. Both pure and complicated form of HSP can be found. The variant c.316G &amp;gt; A is a hotspot mutation, and the novel variant c.126C &amp;gt; G expands the mutational spectrum. The phenomenon of <jats:italic>de novo<\/jats:italic> mutations in <jats:italic>NIPA1<\/jats:italic> emphasizes the need to consider autosomal dominant HSP-related genes in sporadic patients.<\/jats:p>","DOI":"10.3389\/fgene.2022.859688","type":"journal-article","created":{"date-parts":[[2022,4,8]],"date-time":"2022-04-08T05:19:10Z","timestamp":1649395150000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Clinical and Genetic Features of Chinese Patients With NIPA1-Related Hereditary Spastic Paraplegia Type 6"],"prefix":"10.3389","volume":"13","author":[{"given":"Jun","family":"Fu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingming","family":"Ma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiewen","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,4,8]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e2","DOI":"10.1111\/ene.12284","article-title":"Pure Hereditary Spastic Paraplegia Due to Ade Novomutation in theNIPA1gene","volume":"21","author":"Arkadir","year":"2014","journal-title":"Eur. 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