{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T23:16:29Z","timestamp":1782947789273,"version":"3.54.5"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T00:00:00Z","timestamp":1782950400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Genet."],"abstract":"<jats:p>\n                    Hereditary spastic paraplegia (HSP) comprises a group of neurodegenerative disorders characterized by progressive spasticity of the lower limbs. Troyer syndrome (MIM #275900), an autosomal recessive form of complicated HSP, was initially described in the Old Order Amish population. The syndrome is associated with a spectrum of clinical manifestations, including spastic paraplegia, muscle atrophy, dysarthria, intellectual disability, and abnormal white matter on neuroimaging. The causative gene for Troyer syndrome has been identified as\n                    <jats:italic>SPG20<\/jats:italic>\n                    , which encodes the spartin protein. Spartin plays a pivotal role in lipid droplet degradation and mitochondrial function. Here, we report the clinical and molecular features of the second documented case of Troyer syndrome in China. The patient, a 5-year-8-month-old Han Chinese girl, presented with delayed psychomotor development, abnormal gait, and a history of febrile seizures. Whole-exome sequencing revealed a novel homozygous pathogenic variant, c.1734-1G&amp;gt;C, in\n                    <jats:italic>SPG20<\/jats:italic>\n                    , leading to a frameshift and the expression of a truncated protein. This variant was absent from multiple population databases of healthy individuals, and both parents were heterozygous carriers without clinical manifestations. Functional studies in cells transfected with\n                    <jats:italic>SPG20<\/jats:italic>\n                    constructs demonstrated that the variant spartin protein failed to localize to lipid droplets, leading to their accumulation. This functional impairment may contribute to the pathogenesis of Troyer syndrome. Our findings expand the variant spectrum of\n                    <jats:italic>SPG20<\/jats:italic>\n                    and provide further insight into the genotype\u2013phenotype relationship in Troyer syndrome, highlighting the critical role of spartin in lipid metabolism and neuronal function.\n                  <\/jats:p>","DOI":"10.3389\/fgene.2026.1842902","type":"journal-article","created":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T22:10:30Z","timestamp":1782943830000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Novel homozygous pathogenic variant of the SPG20 gene causes the Troyer syndrome in China"],"prefix":"10.3389","volume":"17","author":[{"given":"Lina","family":"Zhu","sequence":"first","affiliation":[{"name":"Senior Department of Pediatrics, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Hu","sequence":"additional","affiliation":[{"name":"Senior Department of Pediatrics, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyang","family":"Jiang","sequence":"additional","affiliation":[{"name":"Senior Department of Pediatrics, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rujie","family":"Gu","sequence":"additional","affiliation":[{"name":"Senior Department of Pediatrics, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongxia","family":"Wang","sequence":"additional","affiliation":[{"name":"Senior Department of Pediatrics, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shufang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Senior Department of Pediatrics, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fujun","family":"Peng","sequence":"additional","affiliation":[{"name":"Weifang Key Laboratory of Collaborative Innovation of Intelligent Diagnosis and Treatment and Molecular Diseases, School of Basic Medical Sciences, Shandong Second Medical University","place":["Weifang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiuwei","family":"Ma","sequence":"additional","affiliation":[{"name":"Senior Department of Pediatrics, The Seventh Medical Center of Chinese PLA General Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1780","DOI":"10.1002\/ajmg.a.37658","article-title":"Three cases of troyer syndrome in two families of Filipino descent","volume":"170","author":"Butler","year":"2016","journal-title":"Am. 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A recessive form of spastic paraplegia with distal muscle wasting","volume":"16","author":"Cross","year":"1967","journal-title":"Archives Neurology"},{"key":"B6","doi-asserted-by":"publisher","first-page":"188813","DOI":"10.1016\/j.bbcan.2022.188813","article-title":"Spartin: at the crossroad between ubiquitination and metabolism in cancer","volume":"1877","author":"Cusenza","year":"2022","journal-title":"Biochimica Biophysica Acta Rev. cancer"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/mcs.a001537","article-title":"SPG20 mutation in three siblings with familial hereditary spastic paraplegia","volume":"3","author":"Dardour","year":"2017","journal-title":"Cold Spring Harb. molecular case studies"},{"key":"B8","doi-asserted-by":"publisher","first-page":"230040","DOI":"10.1098\/rsob.230040","article-title":"Mutant SPART causes defects in mitochondrial protein import and bioenergetics reversed by coenzyme Q","volume":"13","author":"Diquigiovanni","year":"2023","journal-title":"Open biology"},{"key":"B9","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1083\/jcb.200808041","article-title":"A role for ubiquitin ligases and Spartin\/SPG20 in lipid droplet turnover","volume":"184","author":"Eastman","year":"2009","journal-title":"J. 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A clinical and radiological study of a complicated hereditary spastic paraplegia","volume":"251","author":"Proukakis","year":"2004","journal-title":"J. Neurology"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1093\/hmg\/dds191","article-title":"Spg20-\/- mice reveal multimodal functions for troyer syndrome protein spartin in lipid droplet maintenance, cytokinesis and BMP signaling","volume":"21","author":"Renvois\u00e9","year":"2012","journal-title":"Hum. 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United States of America"}],"container-title":["Frontiers in Genetics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1842902\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T22:10:34Z","timestamp":1782943834000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fgene.2026.1842902\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,2]]},"references-count":20,"alternative-id":["10.3389\/fgene.2026.1842902"],"URL":"https:\/\/doi.org\/10.3389\/fgene.2026.1842902","relation":{},"ISSN":["1664-8021"],"issn-type":[{"value":"1664-8021","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,2]]},"article-number":"1842902"}}