{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T22:46:47Z","timestamp":1774824407198,"version":"3.50.1"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,30]],"date-time":"2026-03-30T00:00:00Z","timestamp":1774828800000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Mutations in the\n                      <jats:italic>SPAST<\/jats:italic>\n                      gene cause autosomal dominant hereditary spastic paraplegia (HSP) type 4 (SPG4), which is the most common type of HSP with variable frequencies in different ethnic backgrounds. The clinical and genetic characteristics of SPG4 in Central China have not been well documented.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We screened for\n                      <jats:italic>SPAST<\/jats:italic>\n                      variants by whole exome sequencing in a cohort of 63 unrelated families with HSP from Central China. The clinical manifestations were evaluated.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      21 variants of\n                      <jats:italic>SPAST<\/jats:italic>\n                      were identified in 21 index patients with a frequency of 33.3% (21\/63). Seven novel variants were identified, including one missense variant (p.S399W), five frameshift variants (p.Q170Vfs*2, p.S527Vfs*3, p.I605Vfs*17, p.I605Nfs*26, and p.V443Afs*2), and one splicing variant (c.871-1G&amp;gt;A). We also detected four previously reported exon deletions of\n                      <jats:italic>SPAST<\/jats:italic>\n                      . The mean age of disease onset was 34.0\u00a0years. Anticipation and variability of disease severity were observed in some autosomal dominant families. Two patients exhibited a complicated phenotype, one of whom presented with hyposmia, which had never been previously reported with SPG4.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      SPG4 is the most common type of HSP in our cohort. Complicated phenotype, although rare, can also be observed in SPG4 patients. The hyposmia might be a new phenotype associated with SPG4. The\n                      <jats:italic>SPAST<\/jats:italic>\n                      rearrangement is common and should be considered during genetic analysis. The novel\n                      <jats:italic>SPAST<\/jats:italic>\n                      variants identified in this study expand the mutational spectrum.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fgene.2026.1800987","type":"journal-article","created":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T22:10:20Z","timestamp":1774822220000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Expanding the clinical and mutational spectrum of hereditary spastic paraplegia type 4 in a cohort of patients from central China"],"prefix":"10.3389","volume":"17","author":[{"given":"Jun","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Neurology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jia","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gang","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi","family":"Pang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jiewen","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mingming","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Neurology, Henan Provincial People\u2019s Hospital","place":["Zhengzhou, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1186\/1471-2377-10-89","article-title":"Mutational spectrum of the SPG4 (SPAST) and SPG3A (ATL1) genes in Spanish patients with hereditary spastic paraplegia","volume":"10","author":"Alvarez","year":"2010","journal-title":"BMC Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1016\/j.jns.2016.03.018","article-title":"Genetic background of the hereditary spastic paraplegia phenotypes in Hungary - an analysis of 58 probands","volume":"364","author":"Balicza","year":"2016","journal-title":"J. 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