SURF1 related Leigh syndrome: Clinical and molecular findings of 16 patients from Turkey

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dc.contributor.authorKose, Melis
dc.contributor.authorCanda, Ebru
dc.contributor.authorKagnici, Mehtap
dc.contributor.authorAykut, Ayca
dc.contributor.authorAdebali, Ogun
dc.contributor.authorDurmaz, Asude
dc.contributor.authorUnalp, Aycan
dc.date.accessioned2021-05-03T20:36:45Z
dc.date.available2021-05-03T20:36:45Z
dc.date.issued2020
dc.departmentEge Üniversitesien_US
dc.description.abstractIntroduction: Pathogenic variants in SURF1, a nuclear-encoded gene encoding a mitochondrial chaperone involved in COX assembly, are one of the most common causes of Leigh syndrome (LS). Material-methods: Sixteen patients diagnosed to have SURF1-related LS between 2012 and 2020 were included in the study. Their clinical, biochemical and molecular findings were recorded. 10/16 patients were diagnosed using whole-exome sequencing (WES), 4/16 by Sanger sequencing of SURF1, 1/16 via targeted exome sequencing and 1/16 patient with whole-genome sequencing (WGS). The pathogenicity of SURF1 variants was evaluated by phylogenetic studies and modelling on the 3D structure of the SURF1 protein. Results: We identified 16 patients from 14 unrelated families who were either homozygous or compound heterozygous for SURF1 pathogenic variants. Nine different SURF1 variants were detected The c.769G > A was the most common variant with an allelic frequency of 42.8% (12/28), c.870dupT [(p.Lys291*); (8/28 28.5%)], c.169deIG [(p.Glu57 Lysfs*15), (2/24; 7.1%)], c.532 T > A [(p.Tyr178Asn); (2/28, 7.1%)], c.653_654delCT [(p.Pro218Argfs*29); (4/28, 14.2%)] c.595_597de1GGA [(p.Gly199del); (1/28, 3.5%)], c.751 + 1G > A (2/28, 4.1%), c.356C > T [(p.Pro119Leu); (2/28, 3.5%)] were the other detected variants. Two pathogenic variants, C.595_597delGGA and c.356C > T, were detected for the first time. The c.769 G > A variant detected in 6 patients from 5 families was evaluated in terms of phenotype-genotype correlation. There was no definite genotype - phenotype correlation. Conclusions: To date, more than 120 patients of LS with SURF1 pathogenic variants have been reported. We shared the clinical, molecular data and natural course of 16 new SURF1 defect patients from our country. This study is the first comprehensive research from Turkey that provides information about disease-causing variants in the SURF1 gene. The identification of common variants and phenotype of the SURF1 gene is important for understanding SURF1 related LS. Synopsis: SURF1 gene defects are one of the most important causes of LS; patients have a homogeneous clinical and biochemical phenotype.en_US
dc.description.sponsorshipWellcome Centre for Mitochondrial Research [203105/Z/16/Z]; Medical Research Council (MRC) International Centre for Genomic Medicine in Neuromuscular DiseaseUK Research & Innovation (UKRI)Medical Research Council UK (MRC); Mitochondrial Disease Patient Cohort (UK) [G0800674]; Newcastle University Centre for Ageing and Vitality; Biotechnology and Biological Sciences Research Council and Medical Research CouncilUK Research & Innovation (UKRI)Biotechnology and Biological Sciences Research Council (BBSRC)Medical Research Council UK (MRC) [L016354]; UK NIHR Biomedical Research Centre for Ageing and Age-related disease award; Lily Foundation; UK NHS Specialist Commissioners; European Molecular Biology Organization (EMBO) - Scientific and Technological Research Council of Turkey (TUBITAK); Science Academy, Turkey; TUBITAK International Fellowship for Outstanding Researchers ProgrammeTurkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK)en_US
dc.description.sponsorshipRM and RWT are supported by the Wellcome Centre for Mitochondrial Research (203105/Z/16/Z), the Medical Research Council (MRC) International Centre for Genomic Medicine in Neuromuscular Disease, the Mitochondrial Disease Patient Cohort (UK) (G0800674), Newcastle University Centre for Ageing and Vitality (supported by the Biotechnology and Biological Sciences Research Council and Medical Research Council L016354), UK NIHR Biomedical Research Centre for Ageing and Age-related disease award to the Newcastle upon Tyne Hospitals NHS Foundation Trust, the Lily Foundation and the UK NHS Specialist Commissioners which funds the "Rare Mitochondrial Disorders of Adults and Children" Diagnostic Service in Newcastle upon Tyne (http://www.newcastle-mitochondria.com.OA is supported by the European Molecular Biology Organization (EMBO) Installation grant funded by the Scientific and Technological Research Council of Turkey (TUBITAK); Science Academy, Turkey; TUBITAK International Fellowship for Outstanding Researchers Programme.en_US
dc.identifier.doi10.1016/j.ymgmr.2020.100657en_US
dc.identifier.issn2214-4269
dc.identifier.pmid33134083en_US
dc.identifier.urihttps://doi.org/10.1016/j.ymgmr.2020.100657
dc.identifier.urihttps://hdl.handle.net/11454/70190
dc.identifier.volume25en_US
dc.identifier.wosWOS:000600655200023en_US
dc.identifier.wosqualityN/Aen_US
dc.indekslendigikaynakWeb of Scienceen_US
dc.indekslendigikaynakPubMeden_US
dc.language.isoenen_US
dc.publisherElsevieren_US
dc.relation.ispartofMolecular Genetics and Metabolism Reportsen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanıen_US
dc.rightsinfo:eu-repo/semantics/openAccessen_US
dc.subjectCOX deficiencyen_US
dc.subjectLeigh syndromeen_US
dc.subjectNeuroregressionen_US
dc.subjectNext-generation sequencingen_US
dc.subjectNuclear mitochondrial disordersen_US
dc.subjectSURF1 geneen_US
dc.titleSURF1 related Leigh syndrome: Clinical and molecular findings of 16 patients from Turkeyen_US
dc.typeArticleen_US

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