Mitochondrial translation is essential for the biogenesis of the mitochondrial oxidative phosphorylation system (OXPHOS) that synthesizes the bulk of ATP for the cell. Hypomorphic and loss-of-function variants in either mitochondrial DNA or in nuclear genes that encode mitochondrial translation factors can result in impaired OXPHOS biogenesis and mitochondrial diseases with variable clinical presentations. Compound heterozygous or homozygous missense and frameshift variants in the FARS2 gene, that encodes the mitochondrial phenylalanyl-tRNA synthetase, are commonly linked to either early-onset epileptic mitochondrial encephalopathy or spastic paraplegia. Here, we expand the genetic spectrum of FARS2-linked disease with three patients carrying novel compound heterozygous variants in the FARS2 gene and presenting with spastic tetraparesis, axial hypotonia and myoclonic epilepsy in two cases.

线粒体翻译对于为细胞合成大量 ATP 的线粒体氧化磷酸化系统 (OXPHOS) 的生物发生至关重要。线粒体 DNA 或编码线粒体翻译因子的核基因中的亚型和功能丧失变异可导致 OXPHOS 生物发生受损和具有不同临床表现的线粒体疾病。FARS2基因中的复合杂合或纯合错义和移码变体编码线粒体苯丙氨酰-tRNA 合成酶，通常与早发性癫痫性线粒体脑病或痉挛性截瘫有关。在这里，我们扩展了FARS2的遗传谱与三名携带FARS2基因新型复合杂合变异体的患者相关的疾病，并在两例中出现痉挛性四肢轻瘫、轴性肌张力减退和肌阵挛性癫痫。