Likely inborn error of metabolism

Gene: FAR1

The rating of this gene has been updated following NHS Genomic Medicine Serviceapproval.

Created: 14 Mar 2022, 2:05 p.m. | Last Modified: 14 Mar 2022, 2:05 p.m.

Panel Version: 2.229

Red List (low evidence)

Comment on list classification: In view of the normal metabolic screening (excluding very specific functional work, which will not be in routine NHS practice) there is no clear alignment with the metabolic panels and therefore FAR1 should be demoted from Green to Red at the next GMS panel update (discussed with Helen Brittain, Genomic England Clinical Team)

Created: 28 Jun 2021, 11:55 a.m. | Last Modified: 28 Jun 2021, 11:55 a.m.

Panel Version: 2.144

Associated with relevant phenotype in OMIM and has a 'confirmed' disease confidence rating for 'Severe intellectual disability, epilepsy, and cataracts' in Gene2Phenotype.

Both biallelic (PMIDs: 25439727; 30561787) and monoallelic variants (PMID: 33239752) have been linked to disease; both supported by functional data but showing distinct biochemical phenotypes. FAR1-deficient patients had a profound deficiency of plasmalogens whereas the patients with the heterozygous de novo variants had elevated levels of ether lipids, including plasmalogens. Both MOI's are associated with similar phenotypes including DD/ID, spasticity, cataracts, and seizures.

All individuals (both mono- and biallelic cases) that has undergone metabolic investigations had normal results.

Created: 28 Jun 2021, 11:51 a.m. | Last Modified: 28 Jun 2021, 11:51 a.m.

Panel Version: 2.143

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154

Publications

• 25439727
• 30561787
• 33239752