Wellcome Centre for Mitochondrial Research Institute of Neuroscience Newcastle University Newcastle upon Tyne United Kingdom.
Department of Neurology Erasmus Medical Centre Rotterdam Netherlands.
Ann Clin Transl Neurol. 2019 Feb 17;6(3):515-524. doi: 10.1002/acn3.725. eCollection 2019 Mar.
Mitochondrial methionyl-tRNA formyltransferase (MTFMT) is required for the initiation of translation and elongation of mitochondrial protein synthesis Pathogenic variants in have been associated with Leigh syndrome (LS) and mitochondrial multiple respiratory chain deficiencies. We sought to elucidate the spectrum of clinical, neuroradiological and molecular genetic findings of patients with bi-allelic pathogenic variants in .
Retrospective cohort study combining new cases and previously published cases.
Thirty-eight patients with pathogenic variants in were identified, including eight new cases. The median age of presentation was 14 months (range: birth to 17 years, interquartile range [IQR] 4.5 years), with developmental delay and motor symptoms being the most frequent initial manifestation. Twenty-nine percent of the patients survived into adulthood. MRI headings in pathogenic variants included symmetrical basal ganglia changes (62%), periventricular and subcortical white matter abnormalities (55%), and brainstem lesions (48%). Isolated complex I and combined respiratory chain deficiencies were identified in 31% and 59% of the cases, respectively. Reduction of the mitochondrial complex I and complex IV subunits was identified in the fibroblasts (13/13). Sixteen pathogenic variants were identified, of which c.626C>T was the most common. Seventy-four percent of the patients were alive at their last clinical review (median 6.8 years, range: 14 months to 31 years, IQR 14.5 years).
Patients that harbour pathogenic variants in have a milder clinical phenotype and disease progression compared to LS caused by other nuclear defects. Fibroblasts may preclude the need for muscle biopsy, to prove causality of any novel variant.
线粒体甲硫氨酰-tRNA 甲酰转移酶（MTFMT）是翻译起始和线粒体蛋白合成延伸所必需的。已经发现 中的致病性变异与 Leigh 综合征（LS）和线粒体多呼吸链缺陷有关。我们试图阐明双等位基因致病性变异患者的临床、神经放射学和分子遗传学特征。
回顾性队列研究，结合新病例和以前发表的病例。
共发现 38 例 中的致病性变异患者，包括 8 例新病例。发病年龄中位数为 14 个月（范围：出生至 17 岁，四分位距 [IQR] 4.5 岁），以发育迟缓伴运动症状为最常见首发表现。29%的患者存活至成年。致病性变异患者的 MRI 头部表现包括对称性基底节改变（62%）、脑室周围和皮质下白质异常（55%）和脑干病变（48%）。31%的病例分别存在孤立的复合物 I 和综合呼吸链缺陷，59%的病例存在综合呼吸链缺陷。在 13/13 的成纤维细胞中发现了线粒体复合物 I 和复合物 IV 亚基的减少。共发现 16 种致病性变异，其中最常见的是 c.626C>T。16 例患者中，74%在最后一次临床随访时仍存活（中位时间 6.8 年，范围：14 个月至 31 岁，IQR 14.5 年）。
与其他核缺陷引起的 LS 相比，携带 中的致病性变异的患者具有更轻微的临床表型和疾病进展。成纤维细胞可能排除了肌肉活检的需要，以证明任何新变异的因果关系。
