Scala Marcello, Brigati Giorgia, Fiorillo Chiara, Nesti Claudia, Rubegni Anna, Pedemonte Marina, Bruno Claudio, Severino Mariasavina, Derchi Maria, Minetti Carlo, Santorelli F M
Department of Pediatric Neurology and Muscular Disorders, IRCCS Istituto Giannina Gaslini, Via Gerolamo Gaslini, 5, 16147, Genoa, Italy.
University of Genoa, Genoa, Italy.
Neurogenetics. 2019 Aug;20(3):165-172. doi: 10.1007/s10048-019-00582-5. Epub 2019 Jul 2.
TSFM is a nuclear gene encoding the elongation factor Ts (EFTs), an essential component of mitochondrial translational machinery. Impaired mitochondrial translation is responsible for neurodegenerative disorders characterized by multiple respiratory chain complex defects, multisystemic involvement, and neuroradiological features of Leigh-like syndrome. With the use of a next-generation sequencing (NGS)-based multigene panel for mitochondrial disorders, we identified the novel TSFM homozygous variant c.547G>A (p.Gly183Ser) in a 5-year-old boy with infantile early onset encephalocardiomyopathy, sensorineural hearing loss, and peculiar partially reversible neuroimaging features. Our findings expand the phenotypic spectrum of TSFM-related encephalopathy, offering new insights into the natural history of brain involvement and suggesting that TSFM should be investigated in pediatric mitochondrial disorders with distinctive neurologic and cardiac involvement.
TSFM是一种核基因，编码延伸因子Ts（EFTs），它是线粒体翻译机制的一个重要组成部分。线粒体翻译受损是导致神经退行性疾病的原因，这些疾病的特征是多个呼吸链复合体缺陷、多系统受累以及类似Leigh综合征的神经放射学特征。通过使用基于下一代测序（NGS）的线粒体疾病多基因检测板，我们在一名患有婴儿期早发性脑心肌病、感音神经性听力损失以及特殊的部分可逆性神经影像学特征的5岁男孩中，鉴定出了新的TSFM纯合变异c.547G>A（p.Gly183Ser）。我们的研究结果扩展了TSFM相关脑病的表型谱，为脑部受累的自然史提供了新的见解，并表明在具有独特神经和心脏受累的儿科线粒体疾病中应研究TSFM。
