Confirmation of TACO1 as a Leigh Syndrome Disease Gene in Two Additional Families

Basit Öğe Kaydı
dc.authoridSchöls, Ludger/0000-0001-7774-5025
dc.authoridBender, Benjamin/0000-0002-3205-4631
dc.authoridHorvath, Rita/0000-0002-9841-170X
dc.authoridMunro, Benjamin/0000-0003-4506-7092
dc.authoridOktay, Yavuz/0000-0002-0158-2693
dc.authoridYilmaz, Elmasnur/0000-0001-9711-0203
dc.authoridKamereit, Sofie/0009-0002-8110-740X
dc.authorwosidSchöls, Ludger/ABB-2482-2021
dc.authorwosidBender, Benjamin/AEQ-6456-2022
dc.authorwosidOktay, Yavuz/G-4794-2015
dc.authorwosidSchule, Rebecca/B-5763-2019
dc.contributor.authorOktay, Yavuz
dc.contributor.authorGungor, Serdal
dc.contributor.authorZeltner, Lena
dc.contributor.authorWiethoff, Sarah
dc.contributor.authorSchoels, Ludger
dc.contributor.authorSonmezler, Ece
dc.contributor.authorYilmaz, Elmasnur
dc.date.accessioned2024-08-04T20:47:23Z
dc.date.available2024-08-04T20:47:23Z
dc.date.issued2020
dc.departmentİnönü Üniversitesien_US
dc.description.abstractBackground: In 2009, we identified TACO1 as a novel mitochondrial disease gene in a single family, however no second family has been described to confirm the role of TACO1 in mitochondrial disease. Objective: In this report, we describe two independent consanguineous families carrying pathogenic variants in TACO1, confirming the phenotype. Methods: Detailed clinical investigations and whole exome sequencing with haplotype analysis have been performed in several members of the two reported families. Results: Clinical phenotype of the patients confirms the originally reported phenotype of a childhood-onset progressive cerebellar and pyramidal syndrome with optic atrophy and learning difficulties. Brain MRI showed periventricular white matter lesions with multiple cystic defects, suggesting leukoencephalopathy in both patients. One patient carried the previously described homozygous TACO1 variant (p.His158ProfsTer8) and haplotype analysis suggested that this variant is a rare founder mutation. The second patient from another family carried a homozygous novel frame shift variant (p.Cys85PhefsTer15). Conclusions: The identification of two Turkish families with similar characteristic clinical presentation and an additional homozygous nonsense mutation confirms that TACO1 is a human mitochondrial disease gene. Although most patients with this clinical presentation undergo next generation sequencing analysis, screening for selected founder mutations in the Turkish population based on the precise clinical presentation may reduce time and cost of finding the genetic diagnosis even in the era of massively parallel sequencing.en_US
dc.description.sponsorshipNewton Fund UK/Turkey [MR/N027302/1]; Medical Research Council (UK) [MR/N025431/1]; Wellcome Investigator fund [109915/Z/15/Z]; Lily Foundation UK; European Research Council [309548]; Wellcome Trust Pathfinder Scheme [201064/Z/16/Z]; TUBITAK project [216S771]; Turkish Academy of Sciences (TUBA) Young Investigator Program (TUBA-GEBIP); Horizon 2020 research and innovation program [779257]; Bundesministerium fur Bildung und Forschung (BMBF) [01GM1905]; National Institute of Health (NIH/NINDS) [5R01NS072248]; HSP Selbsthilfegruppe e.V.; Canadian Institutes of Health Research [FDN-167281]; Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C); Canada Foundation for Innovation [CFI-JELF 38412]; Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health) [950-232279]; National Human Genome Research Institute [UM1 HG008900]; National Heart, Lung, and Blood Institute under the Trans-Omics for Precision Medicine (TOPMed) program; National Eye Institute; RD-Connect Genome-Phenome Analysis platform developed under FP7/2007-2013 [305444]; European Reference Network for Rare Neurological Diseases [739510]; Ministry of Science, Research and the Arts of BadenWurttemberg; European Social Fund (ESF) of Baden-Wurttemberg [31-7635 41/67/1]; MRC [MR/N025431/2, MR/N025431/1, MR/N010035/1, G1000848] Funding Source: UKRI; Newton Fund [MR/N027302/2, MR/N027302/1] Funding Source: UKRIen_US
dc.description.sponsorshipThe study was supported by the Newton Fund UK/Turkey (MR/N027302/1 to HL and RH), the Medical Research Council (UK) (MR/N025431/1 to RH), theWellcome Investigator fund (109915/Z/15/Z to RH), the Lily Foundation UK (to RH), the European Research Council (309548 to RH); and the Wellcome Trust Pathfinder Scheme (201064/Z/16/Z to HL and RH), the TUBITAK project 216S771 to SH and YO. YO is supported by Turkish Academy of Sciences (TUBA) Young Investigator Program (TUBA-GEBIP). The study was further supported by the Horizon 2020 research and innovation program via grant 779257 Solve-RD to RS, the Bundesministerium fur Bildung und Forschung (BMBF) via funding for the translational research consortium TreatHSP (https://treatHSP.net) (01GM1905 to RS), the National Institute of Health (NIH/NINDS) (grant 5R01NS072248 to RS and SZ) and the HSP Selbsthilfegruppe e.V. (grant to RS). HL receives support from the Canadian Institutes of Health Research (Foundation Grant FDN-167281), the Canadian Institutes of Health Research and Muscular Dystrophy Canada (Network Catalyst Grant for NMD4C),the Canada Foundation for Innovation (CFI-JELF 38412), and the Canada Research Chairs program (Canada Research Chair in Neuromuscular Genomics and Health, 950-232279).We thank the Broad Institute for carrying out WES. The Broad Center for Mendelian Genomics (UM1 HG008900) is funded by the National Human Genome Research Institute with supplemental funding provided by the National Heart, Lung, and Blood Institute under the Trans-Omics for Precision Medicine (TOPMed) program and the National Eye Institute. Data was analysed using the RD-Connect Genome-Phenome Analysis platform developed under FP7/2007-2013 funded project (grant agreement n. 305444) and using the Genesis platform developed and maintained by the Genesis Foundation (https://www.tgp-foundation.org).Several authors of this publication are members of the European Reference Network for Rare Neurological Diseases -Project ID No 739510 (BB, LS, LZ, RS) and EURO-NMD (HL, RH). SW is supported by the Ministry of Science, Research and the Arts of BadenWurttemberg and the European Social Fund (ESF) of Baden-Wurttemberg (31-7635 41/67/1).en_US
dc.identifier.doi10.3233/JND-200510
dc.identifier.endpage308en_US
dc.identifier.issn2214-3599
dc.identifier.issn2214-3602
dc.identifier.issue3en_US
dc.identifier.pmid32444556en_US
dc.identifier.scopus2-s2.0-85086052644en_US
dc.identifier.scopusqualityQ1en_US
dc.identifier.startpage301en_US
dc.identifier.urihttps://doi.org/10.3233/JND-200510
dc.identifier.urihttps://hdl.handle.net/11616/99340
dc.identifier.volume7en_US
dc.identifier.wosWOS:000685106600010en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakScopusen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherIos Pressen_US
dc.relation.ispartofJournal of Neuromuscular Diseasesen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subject[No Keywords]en_US
dc.titleConfirmation of TACO1 as a Leigh Syndrome Disease Gene in Two Additional Familiesen_US
dc.typeArticleen_US

Dosyalar

Koleksiyon

WoS İndeksli Yayınlar Koleksiyonu
PubMed İndeksli Yayın Koleksiyonu
Scopus İndeksli Yayınlar Koleksiyonu