New insights into the phenotype of FARS2 deficiency.
Swanson, Michael A
Van Hove, Johan
Van Coster, Rudy
Molecular genetics and metabolism
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Vantroys, E., Larson, A., Friederich, M., Knight, K., Swanson, M. A., Powell, C. A., Smet, J., et al. (2017). New insights into the phenotype of FARS2 deficiency.. Molecular genetics and metabolism, 122 (4), 172-181. https://doi.org/10.1016/j.ymgme.2017.10.004
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.
Muscle, Skeletal, Brain, Cells, Cultured, Mitochondria, Fibroblasts, Humans, Epilepsy, Spastic Paraplegia, Hereditary, Amino Acyl-tRNA Synthetases, Phenylalanine-tRNA Ligase, Mitochondrial Proteins, RNA, Transfer, Magnetic Resonance Imaging, Sequence Analysis, DNA, Aminoacylation, Oxygen Consumption, Heterozygote, Phenotype, Mutation, Missense, Adolescent, Infant, Female, Male, Exome
External DOI: https://doi.org/10.1016/j.ymgme.2017.10.004
This record's URL: https://www.repository.cam.ac.uk/handle/1810/276405
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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