相关 Leigh 综合征：来自土耳其的 16 例患者的临床及分子学发现
related Leigh syndrome: Clinical and molecular findings of 16 patients from Turkey.
作者信息
Kose Melis, Canda Ebru, Kagnici Mehtap, Aykut Ayça, Adebali Ogün, Durmaz Asude, Bircan Aylin, Diniz Gulden, Eraslan Cenk, Kose Engin, Ünalp Aycan, Yılmaz Ünsal, Ozyilmaz Berk, Özdemir Taha Reşid, Atik Tahir, Uçar Sema Kalkan, McFarland Robert, Taylor Robert W, Brown Garry K, Çoker Mahmut, Özkınay Ferda
机构信息
Izmir Katip Çelebi University Faculty of Medicine, Department of Pediatrics, Division of Pediatric Metabolism and Nutrition, Izmir, Turkey.
Ege University Faculty of Medicine, Department of Pediatrics, Division of Nutrition and Metabolism, Izmir, Turkey.
出版信息
Mol Genet Metab Rep. 2020 Oct 23;25:100657. doi: 10.1016/j.ymgmr.2020.100657. eCollection 2020 Dec.
INTRODUCTION
Pathogenic variants in , 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 -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 , 1/16 via targeted exome sequencing and 1/16 patient with whole-genome sequencing (WGS). The pathogenicity of 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 pathogenic variants. Nine different 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.Glu57Lysfs15), (2/24; 7.1%)], c.532 T > A [(p.Tyr178Asn); (2/28, 7.1%)], c.653_654delCT [(p.Pro218Argfs29); (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 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 gene. The identification of common variants and phenotype of the 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.
引言
是一个核编码基因，编码一种参与细胞色素c氧化酶（COX）组装的线粒体伴侣蛋白，其致病性变异是 Leigh 综合征（LS）最常见的病因之一。
材料与方法
本研究纳入了 2012 年至 2020 年间确诊患有与 相关的 LS 的 16 例患者。记录了他们的临床、生化和分子学检查结果。16 例患者中，10 例通过全外显子组测序（WES）确诊，4 例通过对 的 Sanger 测序确诊，1 例通过靶向外显子组测序确诊，1 例通过全基因组测序（WGS）确诊。通过系统发育研究和对 SURF1 蛋白三维结构的建模评估了 变异的致病性。
结果
我们从 14 个无关家庭中鉴定出 16 例患者，他们为 致病性变异的纯合子或复合杂合子。检测到 9 种不同的 变异。c.769G＞A 是最常见的变异，等位基因频率为 42.8%（12/28），c.870dupT [（p.Lys291*）；（8/28，28.5%）]，c.169delG [（p.Glu57Lysfs15），（2/24；7.1%）]，c.532T＞A [（p.Tyr178Asn）；（2/28，7.1%）]，c.653_654delCT [（p.Pro218Argfs29）；（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.Pro1,19Leu）；（2/28，3.5%）] 是其他检测到的变异。两种致病性变异，C.595_597delGGA 和 c.356C＞T，首次被检测到。对来自 5 个家庭的 6 例患者中检测到的 c.769G＞A 变异进行了表型 - 基因型相关性评估。没有明确的基因型 - 表型相关性。
结论
迄今为止，已报道了 120 多名患有 致病性变异的 LS 患者。我们分享了我国 16 例新的 SURF1 缺陷患者的临床、分子数据和自然病程。本研究是来自土耳其的第一项全面研究，提供了有关 基因致病变异的信息。鉴定 基因的常见变异和表型对于理解与 SURF1 相关的 LS 很重要。
概要
SURF1 基因缺陷是 LS 的最重要病因之一；患者具有相同的临床和生化表型。
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