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New insights into the phenotype of FARS2 deficiency

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Abstract
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.
Keywords
FARS2, Mitochondria, Mitochondrial aminoacyl-tRNA synthetase, Early-onset epileptic encephalopathy, Hereditary spastic paraplegia, Neurogenic bladder, TRANSFER-RNA SYNTHETASE, C-OXIDASE DEFICIENCY, RESPIRATORY-CHAIN, LEIGH-SYNDROME, MUTATIONS, DISEASE, ENCEPHALOPATHY, DISORDERS, DIAGNOSIS, EPILEPSY

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Citation

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Chicago
Vantroys, Elise, Austin Larson, Marisa Friederich, Kaz Knight, Michael A Swanson, Christopher A Powell, Joél Smet, et al. 2017. “New Insights into the Phenotype of FARS2 Deficiency.” Molecular Genetics and Metabolism 122 (4): 172–181.
APA
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.
Vancouver
1.
Vantroys E, Larson A, Friederich M, Knight K, Swanson MA, Powell CA, et al. New insights into the phenotype of FARS2 deficiency. MOLECULAR GENETICS AND METABOLISM. 2017;122(4):172–81.
MLA
Vantroys, Elise, Austin Larson, Marisa Friederich, et al. “New Insights into the Phenotype of FARS2 Deficiency.” MOLECULAR GENETICS AND METABOLISM 122.4 (2017): 172–181. Print.
@article{8542664,
  abstract     = {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 {\textrangle} T (p.Pro361Leu) was detected in both patients. The mutations c.461C {\textrangle} 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.},
  author       = {Vantroys, Elise and Larson, Austin and Friederich, Marisa and Knight, Kaz and Swanson, Michael A and Powell, Christopher A and Smet, Jo{\'e}l and Vergult, Sarah and De Paepe, Boel and Seneca, Sara and Roeyers, Herbert and Menten, Bj{\"o}rn and Minczuk, Michal and Vanlander, Arnaud and Van Hove, Johan and Van Coster, Rudy},
  issn         = {1096-7192},
  journal      = {MOLECULAR GENETICS AND METABOLISM},
  keyword      = {FARS2,Mitochondria,Mitochondrial aminoacyl-tRNA synthetase,Early-onset epileptic encephalopathy,Hereditary spastic paraplegia,Neurogenic bladder,TRANSFER-RNA SYNTHETASE,C-OXIDASE DEFICIENCY,RESPIRATORY-CHAIN,LEIGH-SYNDROME,MUTATIONS,DISEASE,ENCEPHALOPATHY,DISORDERS,DIAGNOSIS,EPILEPSY},
  language     = {eng},
  number       = {4},
  pages        = {172--181},
  title        = {New insights into the phenotype of FARS2 deficiency},
  url          = {http://dx.doi.org/10.1016/j.ymgme.2017.10.004},
  volume       = {122},
  year         = {2017},
}

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