Intellectual disability - microarray and sequencing
Gene: FAR1
As the recommendation is to change the MOI on this panel, the to_be_confirmed_NHSE tag has been added, as further NHSE review is required.Created: 15 Mar 2022, 6 p.m. | Last Modified: 15 Mar 2022, 6 p.m.
Panel Version: 3.1519
Mode of inheritance
BOTH monoallelic and biallelic (but BIALLELIC mutations cause a more SEVERE disease form), autosomal or pseudoautosomal
Publications
FAR1 was reassessed in view of recent review by Zornitza Stark highlighting newly published cases with heterozygous variants in this gene (PMID: 33239752). While 10/12 patients presented speech delay (later resolved in most cases), neurocognitive delay and ID was less common in the cohort (3/12). The phenotype is better defined by other features such as bilateral cataracts and spastic di- or paraparesis (FAR1 added to the appropriate panels).
This panel is more pertinent to the phenotype associated with biallelic variants, where all individuals presented profound ID (PMID: 25439727; 30561787).
Nonetheless, as there are sufficient cases with monoallelic variants and ID (3), this gene will be flagged for GMS expert review to determine whether there is enough evidence to change the MOI on this panel from 'Biallelic' to 'Both mono- and biallelic'Created: 4 May 2021, 12:35 p.m. | Last Modified: 4 May 2021, 12:35 p.m.
Panel Version: 3.1055
Publications
PMID 33239752: 12 patients with paediatric onset spastic paraparesis and bilateral congenital/juvenile cataracts. Most also had speech and gross motor developmental delay and truncal hypotonia. Exome sequencing identified de novo variants affecting the Arg480 residue in FAR1 (p.Arg480Cys/His/Leu). Further functional studies in fibroblasts showed that these variants cause a disruption of the plasmalogen-dependent feedback regulation of FAR1 protein levels leading to uncontrolled ether lipid production.Created: 19 Apr 2021, 8:51 a.m. | Last Modified: 19 Apr 2021, 8:51 a.m.
Panel Version: 3.1018
Onset in infancy of severely delayed psychomotor development, growth retardation with microcephaly and seizures in 3 individuals from 2 families. Bialleleic variants identified in FAR1 (hom indel in consang family and compound het for a missense and a nonsense) and in vitro expression studies showed that all the variants resulted in a complete loss of enzyme activity.Created: 2 Feb 2020, 8:31 a.m. | Last Modified: 2 Feb 2020, 8:31 a.m.
Panel Version: 3.0
Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes
Peroxisomal fatty acyl-CoA reductase 1 disorder, MIM#616154; spastic paraparesis and bilateral cataracts
Publications
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
SEVERE INTELLECTUAL DISABILITY, EPILEPSY, AND CATARACTS
Publications
This is a pertinent gene from the NIHR BioResource - Rare Diseases Study (NIHRBR-RD) BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene is on the SPEED_NEURO_20170705 gene list. Evidences used for SPEED NEURO gene list: in_ddg2p_20141118_conf;in_ddg2p_20141118_conf;in_ddg2p_201507;in_ddg2p_201507_conf;in_ddg2p_2_4_2017;in_ddg2p_2_4_2017_conf . Main mutation mechanism : Loss of functionCreated: 27 Jul 2017, 5:45 p.m.
Evidences key, gene present in following gene lists and main mutation mechanism : ddg2p_20141118; ddg2p_20141118_conf; ddg2p_201507; ddg2p_201507_conf; GEL_ID_green_20160217; neuro_20160418_strict; Loss of function. This is a pertinent gene from the BRIDGE Study : SPEED (Specialist Pathology: Evaluating Exomes in Diagnostics) which covers epilepsies, movement and microcephaly disorders, this gene comes from the SPEED_NEURO_v3.0_20170404 gene list. The following experts from the BRIDGE consortium NIHRBR-RD contributed to this panel: - Professor F. Lucy Raymond, Cambridge Institute for Medical Research, University of Cambridge - Manju Kurian, Paediatric neurologist, Great Ormond Street Hosptial - Keren Carss, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Alba Sanchis-Juan, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Marie Erwood NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation Trust - Louise Daugherty, NIHR BioResource - Rare Diseases, Cambridge University Hospitals NHS Foundation TrustCreated: 19 Jul 2017, 12:25 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Tag Q2_21_expert_review was removed from gene: FAR1. Tag Q2_21_MOI was removed from gene: FAR1.
Tag to_be_confirmed_NHSE tag was added to gene: FAR1.
Publications for gene: FAR1 were set to 25439727
Tag Q2_21_expert_review tag was added to gene: FAR1. Tag Q2_21_MOI tag was added to gene: FAR1.
Publications for gene: FAR1 were set to 0
Phenotypes for gene: FAR1 were changed from SEVERE INTELLECTUAL DISABILITY, EPILEPSY, AND CATARACTS to Peroxisomal fatty acyl-CoA reductase 1 disorder, OMIM:616154
Source Victorian Clinical Genetics Services was added to FAR1.
12.03.2018: Due to major updates completed (Phase 1, 2 and 3), this panel was promoted to Version 2 in order to reflect the major updates since November 2017 which have resulted in reviews for 836 genes added by Genomics England Curators and the Clinical Team, 130 new Green genes added to the interpretation pipeline (from 751 to 881 Green genes), and the gene total has increased from 1879 to 1927.
The Gel status was updated for this whole panel
The Gel status was updated for this whole panel
FAR1 was added to Intellectual disabilitypanel. Sources: Expert Review Green
FAR1 was created by ellenmcdonagh