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

Kose, Melis and Canda, Ebru and Kagnici, Mehtap and Aykut, Ayça and Adebali, Ogün and Durmaz, Asude and Bircan, Aylin and Diniz, Gulden and Eraslan, Cenk and Kose, Engin and Ünalp, Aycan and Yılmaz, Ünsal and Ozyilmaz, Berk and Özdemir, Taha Reşid and Atik, Tahir and Uçar, Sema Kalkan and McFarland, Robert and Taylor, Robert W. and Brown, Garry K. and Çoker, Mahmut and Özkınay, Ferda (2020) SURF1 related Leigh syndrome: clinical and molecular findings of 16 patients from Turkey. Molecular Genetics and Metabolism Reports, 25 . ISSN 2214-4269

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Introduction: 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.169delG [(p.Glu57Lysfs*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_597delGGA [(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.
Item Type: Article
Uncontrolled Keywords: COX deficiency; Leigh syndrome; Neuroregression; Next-generation sequencing; Nuclear mitochondrial disorders; SURF1 gene
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Ogün Adebali
Date Deposited: 04 Aug 2023 14:49
Last Modified: 04 Aug 2023 14:49

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