Department of Pediatric Neurology and Metabolism, Ghent University Hospital, Ghent, Belgium.
Department of Pediatrics, Section of Clinical Genetics and Metabolism, University of Colorado School of Medicine, Aurora, CO, USA.
Mol Genet Metab. 2017 Dec;122(4):172-181. doi: 10.1016/j.ymgme.2017.10.004. Epub 2017 Oct 12.
Mutations in FARS2 are known to cause dysfunction of mitochondrial translation due to deficient aminoacylation of the mitochondrial phenylalanine tRNA. Here, we report three novel mutations in FARS2 found in two patients in a compound heterozygous state. The missense mutation c.1082C>T (p.Pro361Leu) was detected in both patients. The mutations c.461C>T (p.Ala154Val) and c.521_523delTGG (p.Val174del) were each detected in one patient. We report abnormal in vitro aminoacylation assays as a functional validation of the molecular genetic findings. Based on the phenotypic data of previously reported subjects and the two subjects reported here, we conclude that FARS2 deficiency can be associated with two phenotypes: (i) an epileptic phenotype, and (ii) a spastic paraplegia phenotype.
已知 FARS2 基因突变会导致线粒体翻译功能障碍，因为线粒体苯丙氨酸 tRNA 的氨酰化不足。在这里，我们报告了在两名复合杂合状态的患者中发现的 FARS2 的三个新突变。在这两名患者中均检测到错义突变 c.1082C>T（p.Pro361Leu）。突变 c.461C>T（p.Ala154Val）和 c.521_523delTGG（p.Val174del）分别在一名患者中被检测到。我们报告了异常的体外氨酰化测定作为分子遗传学发现的功能验证。基于先前报道的受试者和这里报告的两个受试者的表型数据，我们得出结论，FARS2 缺乏症可能与两种表型相关：（i）癫痫表型，和（ii）痉挛性截瘫表型。
