{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:05:26Z","timestamp":1787065526816,"version":"build-2736575974"},"reference-count":22,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82171238"],"award-info":[{"award-number":["82171238"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82201513"],"award-info":[{"award-number":["82201513"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["CNS Neurosci Ther"],"published-print":{"date-parts":[[2024,4]]},"abstract":"Abstract<\/jats:title>\n \n Introduction<\/jats:title>\n \n Hereditary spastic paraplegias (HSPs) comprise a group of neurodegenerative disorders characterized by progressive degeneration of upper motor neurons. Homozygous or compound heterozygous variants in\n COQ4<\/jats:italic>\n have been reported to cause primary CoQ10 deficiency\u20107 (COQ10D7), which is a mitochondrial disease.\n <\/jats:p>\n <\/jats:sec>\n \n Aims<\/jats:title>\n \n We aimed to screened\n COQ4<\/jats:italic>\n variants in a cohort of HSP patients.\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n A total of 87 genetically unidentified HSP index patients and their available family members were recruited. Whole exome sequencing (WES) was performed in all probands. Functional studies were performed to identify the pathogenicity of those uncertain significance variants.<\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n In this study, five different\n COQ4<\/jats:italic>\n variants were identified in three Chinese HSP pedigrees and two variants were novel, c.87dupT (p.Arg30*), c.304C>T (p.Arg102Cys). More importantly, we firstly described two early\u2010onset pure HSP caused by\n COQ4<\/jats:italic>\n variants. Functional studies in patient\u2010derived fibroblast lines revealed a reduction cellular CoQ10 levels and the abnormal mitochondrial structure.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n Our findings revealed that bilateral variants in the\n COQ4<\/jats:italic>\n gene caused HSP predominant phenotype, expanding the phenotypic spectrum of the COQ4\u2010related disorders.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/cns.14529","type":"journal-article","created":{"date-parts":[[2023,11,28]],"date-time":"2023-11-28T02:20:56Z","timestamp":1701138056000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Biallelic variants in the\n COQ4<\/i>\n gene caused hereditary spastic paraplegia predominant phenotype"],"prefix":"10.1111","volume":"30","author":[{"given":"Qiao","family":"Wei","sequence":"first","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hao","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pei\u2010Shan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan\u2010Juan","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai\u2010Lin","family":"Dong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2106-572X","authenticated-orcid":false,"given":"Zhi\u2010Ying","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou Zhejiang China"},{"name":"Nanhu Brain\u2010computer Interface Institute Hangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2203-0046","authenticated-orcid":false,"given":"Hong\u2010Fu","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics and Center for Rare Diseases, and Department of Neurology in Second Affiliated Hospital, and Key Laboratory of Medical Neurobiology of Zhejiang Province Zhejiang University School of Medicine Hangzhou Zhejiang China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401-013-1115-8"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1474-4422(19)30235-2"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-015-1536-7"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.parkreldis.2020.09.016"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms23031697"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2008.04.172"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2014.12.023"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.776807"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00109-018-1655-4"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40035-019-0157-9"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgg.2021.06.008"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2015.30"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2019.07.016"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-021-10509-6"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-014-9749-9"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2021-107729"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.29167"},{"issue":"11","key":"e_1_2_9_19_1","first-page":"928","article-title":"Primary coenzyme Q10 deficiency\u20107: a case report and literature review","volume":"58","author":"Chen XR","year":"2020","journal-title":"Zhonghua Er Ke Za Zhi"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1038\/s10038-019-0563-y"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41525-019-0091-x"},{"issue":"12","key":"e_1_2_9_22_1","first-page":"1014","article-title":"Clinical characteristics and genetic analysis of primary coenzyme Q10 deficiency caused by COQ4 gene mutation","volume":"35","author":"Ge LL","year":"2019","journal-title":"Chin J Endocrinol Metab"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2022.04.013"}],"container-title":["CNS Neuroscience & 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