Early onset or syndromic epilepsy
Gene: FARS2
AR combined oxidative phosphorylation defic 14 - neonatal onset of dev delay, refractory seizures and lactic acidosis. Shamseldin et al, 2012 - consang S. Arabian family - all 3 sibs had seizures and all died in forst couple of years of life - hom missense variant. Elo et al, 2012 - Finish family - 2 sisters - proband developed treatment-resistant myoclonic seizures on day 2 of life - older sister had a sim phenotype - compound het for two missense variants. Almaki et al 2014 - 2.5 year old boy born of unrelated British Caucasian parents with onset of severe seizures - compound het for missense and an 88kb interstitial del, in vitro studies done. Waker et al, 2016 - girl with severe juvenille-onset epileptic encehalopathy - compound het missense variants and in vitro studies done.Created: 6 Aug 2019, 8:31 p.m. | Last Modified: 6 Aug 2019, 8:31 p.m.
Panel Version: 1.188
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined oxidative phosphorylation deficiency 14, 614946; Spastic paraplegia 77, 617046
Publications
Review and rating collated by Tracy Lester (Oxford Medical Genetics Laboratories Oxford University Hospitals NHS Foundation Trust, 2019_02_06) on behalf of Wessex and West Midlands GLH for GMS Neurology specialist test group, for Clinical Indication R59 'Early onset or syndromic epilepsy'. Review contributors: John Taylor and Helen Lord. Suggested gene rating: Green.Created: 6 Aug 2019, 8:38 p.m. | Last Modified: 6 Aug 2019, 8:38 p.m.
Panel Version: 1.189
Comment on list classification: Updated rating from Amber to Green: Green review by Zornitza- seizures are a common phentoype of MIM:614946. Plenty of unrelated (>3) cases of seizures in FARS2 patients from the literature (PMIDs 24161539, 22833457, 22499341, 28043061) as summarised in PMID:29126765.Created: 29 Nov 2018, 1:59 p.m.
PMID:22499341 (Shamseldin et al 2012) report an index patient and her two siblings with a homozygous FARS2 variant c.431A>G (p.Y144C). The patients had uncontrolled seizures starting in infancy.Created: 29 Nov 2018, 1:54 p.m.
Cho et al, 2017 (PMID:28043061) report a novel homozgyous c.925G>A (G309S) missense variant in FARS2 in 4 patients from 2 nonconsanguineous Korean families. All 4 patients had intractable seizures.Created: 29 Nov 2018, 1:54 p.m.
PMID:22833457 (Elo et al 2012) discovered compound het FARS2 variants in two siblings with fatal epileptic mitochondrial encephalopathy (p.I329T and p.D391V).Created: 29 Nov 2018, 1:53 p.m.
Almalki et al. (2014, PMID: 24161539) report a young boy born to unrelated British Caucasian parents. He demonstrated refractory seizures, developing into focal seizures and had a heterozygous c.973G-T, NM_006567.3 (D325Y) maternally-inherited variant in FARS2 plus a paternally-inherited 88kb deletion of chromosome 6p25.1 including the promotor and UTR of FARS2, and the 3' exons of LYRM4 gene.Created: 29 Nov 2018, 1:53 p.m.
Seizures are a prominent feature of the phenotype.Created: 13 Aug 2018, 12:25 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Combined oxidative phosphorylation deficiency 14, MIM#614946
Publications
Variants in this GENE are reported as part of current diagnostic practice
Source Wessex and West Midlands GLH was added to FARS2.
Source NHS GMS was added to FARS2.
Zornitza Stark: Seizures are a prominent featu
Gene: fars2 has been classified as Green List (High Evidence).
Gene: fars2 has been classified as Green List (High Evidence).
Publications for gene: FARS2 were set to 24161539, 22833457, 22499341, 29126765
Publications for gene: FARS2 were set to
Mode of inheritance for gene: FARS2 was changed from to BIALLELIC, autosomal or pseudoautosomal
Phenotypes for gene: FARS2 were changed from to Combined oxidative phosphorylation deficiency 14, 614946
Expert Review Amber was added to FARS2. Panel: Genetic Epilepsy Syndromes
FARS2 was added to Genetic Epilepsy Syndromes panel. Sources: Victorian Clinical Genetics Services
FARS2 was created by Sarah Leigh