{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T07:53:09Z","timestamp":1789545189565,"version":"build-2803163510"},"reference-count":10,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T00:00:00Z","timestamp":1730246400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Ministry of Science and Higher Education of the Russian Federation","award":["075-15-2021-1061"],"award-info":[{"award-number":["075-15-2021-1061"]}]},{"name":"The Ministry of Science and Higher Education of the Russian Federation","award":["RF 193021X0029"],"award-info":[{"award-number":["RF 193021X0029"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: The SUPV3L1 gene encodes ATP-dependent RNA helicase SUPV3L1, which is a part of the mitochondrial degradosome complex or SUV3. SUPV3L1 unwinds secondary structures of mitochondrial RNA (mtRNA) and facilitates the degradation of mtRNA molecules. A nonsense homozygous variant in the SUPV3L1 gene was recently associated with mitochondrial disease. Our study presents the second documented case of SUPV3L1 pathology in humans. Methods: Whole-genome sequencing was performed on the NovaSeq 6000 platform using pair-end reading. Data analysis was performed with an in-house developed pipeline. Results: The 17-year-old female patient exhibited a diverse array of symptoms, including ataxia, spastic paraparesis, cognitive deficit, optic atrophy, and horizontal gaze-evoked nystagmus. Early onset of symptoms, such as ataxic gait and nystagmus, was noted, with subsequent progression of neurological manifestations. At the time of the observation, the proband had extensive regions of hypopigmented skin patches on the body and extremities, which have progressed over time. Whole-genome sequencing revealed compound heterozygous variants in the SUPV3L1 gene: c.272-2A&gt;G and c.1924A&gt;C; p.(Ser642Arg). RNA analysis demonstrated splicing changes attributable to the c.272-2A&gt;G variant. ELISA assay showed increased Complex I content in the patient\u2019s fibroblasts. This case underscores the phenotypic diversity associated with SUPV3L1 mutations, emphasizing the importance of considering mitochondrial RNA helicase dysfunction in the differential diagnosis of neurodegenerative disorders. Further elucidation of the molecular mechanisms underlying SUPV3L1-associated pathology may provide valuable insights into targeted therapeutic interventions.<\/jats:p>","DOI":"10.3390\/genes15111406","type":"journal-article","created":{"date-parts":[[2024,10,30]],"date-time":"2024-10-30T09:11:24Z","timestamp":1730279484000},"page":"1406","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["A New Case of Mitochondrial RNA Helicase SUPV3L1-Associated Neurodegenerative Disease: Ataxia, Spasticity, Optic Atrophy, and Skin Hypopigmentation (ASOASH)"],"prefix":"10.3390","volume":"15","author":[{"given":"Polina","family":"Tsygankova","sequence":"first","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6519-7375","authenticated-orcid":false,"given":"Denis","family":"Chistol","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7197-3497","authenticated-orcid":false,"given":"Tatiana","family":"Krylova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6594-6126","authenticated-orcid":false,"given":"Igor","family":"Bychkov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vyacheslav","family":"Tabakov","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2672-6294","authenticated-orcid":false,"given":"Tatiana","family":"Markova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elena","family":"Dadali","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Zakharova","sequence":"additional","affiliation":[{"name":"Research Centre for Medical Genetics, Moscow 115552, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,10,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.1093\/nar\/gks1130","article-title":"Human mitochondrial RNA decay mediated by PNPase\u2013hSuv3 complex takes place in distinct foci","volume":"41","author":"Borowski","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"4781","DOI":"10.1021\/bi0356449","article-title":"Purified human SUV3p exhibits multiple-substrate unwinding activity upon conformational change","volume":"43","author":"Shu","year":"2004","journal-title":"Biochemistry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"20812","DOI":"10.1074\/jbc.M109.009605","article-title":"Human mitochondrial SUV3 and polynucleotide phosphorylase form a 330-kDa heteropentamer to cooperatively degrade double-stranded RNA with a 3\u2019-to-5\u2019 directionality","volume":"284","author":"Wang","year":"2009","journal-title":"J. Biol. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1093\/nar\/gkp903","article-title":"Human mitochondrial RNA turnover caught in flagranti: Involvement of hSuv3p helicase in RNA surveillance","volume":"38","author":"Szczesny","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1002\/jimd.12476","article-title":"Mitochondrial RNA processing defect caused by a SUPV3L1 mutation in two siblings with a novel neurodegenerative syndrome","volume":"45","author":"Rodenburg","year":"2022","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_6","unstructured":"(2024, October 01). MaxEntScan Online Programm for Estimation of the Strenght of the Splicing Sites in 3\u2019 Intron Regions. 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Genome"}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/11\/1406\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:24:15Z","timestamp":1760113455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/15\/11\/1406"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,30]]},"references-count":10,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["genes15111406"],"URL":"https:\/\/doi.org\/10.3390\/genes15111406","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,30]]}}}