Hereditary spastic paraplegia

Gene: FARS2

Green List (high evidence)

FARS2 (phenylalanyl-tRNA synthetase 2, mitochondrial)
EnsemblGeneIds (GRCh38): ENSG00000145982
EnsemblGeneIds (GRCh37): ENSG00000145982
OMIM: 611592, Gene2Phenotype
FARS2 is in 13 panels

2 reviews

Rebecca Foulger (Genomics England curator)

Comment on list classification: Updated rating from Grey to Green: Gene added and rated green by Chris Buxton (Bristol NHS). At least 4 unrelated cases of FARS2 variants causing autosomal recessive HSP in the literature (PMIDs 30250868,26553276,25851414,29126765) plus functional support.
Created: 18 Dec 2018, 9:14 a.m.
In 2 unrelated patients with mitochondrial dysfunction and spastic paraplegia, Vantroys et al. (2017, PMID:29126765) identified compound heterozygous variants in the FARS2 gene: (c.1082C-T, NM_006567.4, P361L) in both probands, combined with A154V in proband 1, and a 3-bp deletion (c.521_523delTGG) in proband 2.
Created: 18 Dec 2018, 9:11 a.m.
In 2 sibs with mitochondrial dysfunction and spastic paraplegia, Vernon et al. (2015, PMID:25851414) identified compound het variants in the FARS2 gene: a paternally inherited R419C and a maternally inherited 116-kb interstitial deletion including all of exon 6 and parts of introns 5 and 6.
Created: 18 Dec 2018, 9:11 a.m.
In 4 sibs, born of consanguineous Chinese parents, with AR spastic paraplegia, Yang et al. (2016, PMID:26553276) identified a homozygous transversion (c.424G-T, NM_006567.3) in the FARS2 gene (D142Y).
Created: 18 Dec 2018, 9:11 a.m.
Sahai (2018, PMID:30250868) report a 9‐year‐old boy with novel compound heterozygous variants of FARS2, presenting with a pure spastic paraplegia syndrome: a paternal nonsense variant (Q216X) and a maternal missense variant (P136H).
Created: 18 Dec 2018, 9:11 a.m.

Chris Buxton (North Bristol NHS Trust)

Green List (high evidence)

Sahai (2018, 30250868) FARS2 cpd hhet with pure spastic paraplegia syndrome associated with bilateral signal abnormalities in the dentate nuclei. Biochemical evalutatoin showed impacts on activity of impacted enzyme .

Yang (2016, 26553276), FARS cpd het on exome study, functional studies supportive. Phenotype is Spastic Paraplegia.

Vantroys (2017, 29126765) writes that FARS can be associated with (i) an epileptic phenotype, and (ii) a spastic paraplegia phenotype. Descroibes 2 probands with phenotype including spasticity with cpd het varaints in FARs
Sources: Literature
Created: 27 Nov 2018, 4:53 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
spastic paraplegia

Publications

History Filter Activity

18 Dec 2018, Gel status: 3

Entity classified by Genomics England curator

Rebecca Foulger (Genomics England curator)

Gene: fars2 has been classified as Green List (High Evidence).

18 Dec 2018, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: FARS2 were set to 30250868; 26553276; 29126765

18 Dec 2018, Gel status: 0

Set Phenotypes

Rebecca Foulger (Genomics England curator)

Phenotypes for gene: FARS2 were changed from spastic paraplegia to Spastic paraplegia 77, autosomal recessive, 617046

18 Dec 2018, Gel status: 0

Set publications

Rebecca Foulger (Genomics England curator)

Publications for gene: FARS2 were set to

27 Nov 2018, Gel status: 0

Created, Added New Source, Set mode of inheritance, Set Phenotypes, Set penetrance

Chris Buxton (North Bristol NHS Trust)

gene: FARS2 was added gene: FARS2 was added to Hereditary spastic paraplegia. Sources: Literature Mode of inheritance for gene: FARS2 was set to BIALLELIC, autosomal or pseudoautosomal Phenotypes for gene: FARS2 were set to spastic paraplegia Penetrance for gene: FARS2 were set to unknown Review for gene: FARS2 was set to GREEN