Novel FARS2 variants in patients with early onset encephalopathy with or without epilepsy associated with long survival.
Journal
European journal of human genetics : EJHG
ISSN: 1476-5438
Titre abrégé: Eur J Hum Genet
Pays: England
ID NLM: 9302235
Informations de publication
Date de publication:
03 2021
03 2021
Historique:
received:
02
01
2020
accepted:
20
10
2020
revised:
10
09
2020
pubmed:
11
11
2020
medline:
15
1
2022
entrez:
10
11
2020
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33168986
doi: 10.1038/s41431-020-00757-x
pii: 10.1038/s41431-020-00757-x
pmc: PMC7940479
doi:
Substances chimiques
Mitochondrial Proteins
0
FARS2 protein, human
EC 6.1.1.20
Phenylalanine-tRNA Ligase
EC 6.1.1.20
Types de publication
Case Reports
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
533-538Références
Klipcan L, Levin I, Kessler N, Moor N, Finarov I, Safro M. The tRNA-induced conformational activation of human mitochondrial phenylalanyl-tRNA synthetase. Structure. 2008;16:1095–104.
doi: 10.1016/j.str.2008.03.020
Yadavalli SS, Klipcan L, Zozulya A, Banerjee R, Svergun D, Safro M, et al. Large-scale movement of functional domains facilitates aminoacylation by human mitochondrial phenylalanyl-tRNA synthetase. FEBS Lett. 2009;583:3204–8.
doi: 10.1016/j.febslet.2009.09.008
Elo JM, Yadavalli SS, Euro L, Isohanni P, Gotz A, Carroll CJ, et al. Mitochondrial phenylalanyl-tRNA synthetase mutations underlie fatal infantile Alpers encephalopathy. Hum Mol Genet. 2012;21:4521–9.
doi: 10.1093/hmg/dds294
Shamseldin HE, Alshammari M, Al-Sheddi T, Salih MA, Alkhalidi H, Kentab A, et al. Genomic analysis of mitochondrial diseases in a consanguineous population reveals novel candidate disease genes. J Med Genet. 2012;49:234–41.
doi: 10.1136/jmedgenet-2012-100836
Almalki A, Alston CL, Parker A, Simonic I, Mehta SG, He L, et al. Mutation of the human mitochondrial phenylalanine-tRNA synthetase causes infantile-onset epilepsy and cytochrome c oxidase deficiency. Biochim Biophys Acta. 2014;1842:56–64.
doi: 10.1016/j.bbadis.2013.10.008
Walker MA, Mohler KP, Hopkins KW, Oakley DH, Sweetser DA, Ibba M, et al. Novel compound heterozygous mutations expand the recognized phenotypes of FARS2-linked disease. J Child Neurol. 2016;31:1127–37.
doi: 10.1177/0883073816643402
Raviglione F, Conte G, Ghezzi D, Parazzini C, Righini A, Vergaro R, et al. Clinical findings in a patient with FARS2 mutations and early-infantile-encephalopathy with epilepsy. Am J Med Genet A. 2016;170:3004–7.
doi: 10.1002/ajmg.a.37836
Cho JS, Kim SH, Kim HY, Chung T, Kim D, Jang S, et al. FARS2 mutation and epilepsy: possible link with early-onset epileptic encephalopathy. Epilepsy Res. 2017;129:118–24.
doi: 10.1016/j.eplepsyres.2016.11.022
Vantroys E, Larson A, Friederich M, Knight K, Swanson MA, Powell CA, et al. New insights into the phenotype of FARS2 deficiency. Mol Genet Metab. 2017;122:172–81.
doi: 10.1016/j.ymgme.2017.10.004
Almannai M, Wang J, Dai H, El-Hattab AW, Faqeih EA, Saleh MA, et al. FARS2 deficiency; new cases, review of clinical, biochemical, and molecular spectra, and variants interpretation based on structural, functional, and evolutionary significance. Mol Genet Metab. 2018;125:281–91.
doi: 10.1016/j.ymgme.2018.07.014
Chen Z, Zhang Y. A patient with juvenile-onset refractory status epilepticus caused by two novel compound heterozygous mutations in FARS2 gene. Int J Neurosci. 2019;129:1094–7.
doi: 10.1080/00207454.2019.1634071
Ville D, Lesca G, Labalme A, Portes VD, Arzimanoglou A, de Bellescize J. Early-onset epileptic encephalopathy with migrating focal seizures associated with a FARS2 homozygous nonsense variant. Epileptic Disord. 2020;22:327–35.
doi: 10.1684/epd.2020.1168
Vernon HJ, McClellan R, Batista DA, Naidu S. Mutations in FARS2 and non-fatal mitochondrial dysfunction in two siblings. Am J Med Genet A. 2015;167A:1147–51.
doi: 10.1002/ajmg.a.36993
Yang Y, Liu W, Fang Z, Shi J, Che F, He C, et al. A newly identified missense mutation in FARS2 causes autosomal-recessive spastic paraplegia. Hum Mutat. 2016;37:165–9.
doi: 10.1002/humu.22930
Sahai SK, Steiner RE, Au MG, Graham JM, Salamon N, Ibba M, et al. FARS2 mutations presenting with pure spastic paraplegia and lesions of the dentate nuclei. Ann Clin Transl Neurol. 2018;5:1128–33.
doi: 10.1002/acn3.598
Barcia G, Rio M, Assouline Z, Zangarelli C, Gueguen N, Dumas VD, et al. Clinical, neuroimaging and biochemical findings in patients and patient fibroblasts expressing ten novel GFM1 mutations. Hum Mutat. 2020;41:397–402.
Ruzzenente B, Assouline Z, Barcia G, Rio M, Boddaert N, Munnich A, et al. Inhibition of mitochondrial translation in fibroblasts from a patient expressing the KARS p.(Pro228Leu) variant and presenting with sensorineural deafness, developmental delay, and lactic acidosis. Hum Mutat. 2018;39:2047–59.
doi: 10.1002/humu.23657
Jou C, Ortigoza-Escobar JD, O’Callaghan MM, Nascimento A, Darling A, Pias-Peleteiro L, et al. Muscle involvement in a large cohort of pediatric patients with genetic diagnosis of mitochondrial disease. J Clin Med. 2019;8:68.
Kartvelishvili E, Tworowski D, Vernon H, Moor N, Wang J, Wong LJ, et al. Kinetic and structural changes in HsmtPheRS, induced by pathogenic mutations in human FARS2. Protein Sci. 2017;26:1505–16.
doi: 10.1002/pro.3176