Retinal disordersGene: ARL3
The rating of this gene has been updated following NHS Genomic Medicine Service approval.
Created: 8 Mar 2022, 10:43 a.m. | Last Modified: 8 Mar 2022, 10:43 a.m.
Panel Version: 2.245
This gene is associated with a phenotype in OMIM and Gene2Phenotype (possible - RP, and probable - Joubert syndrome). There is enough evidence to support a gene-disease association for both MOIs. This gene should be rated as Green at the next review.
Created: 18 Oct 2021, 10:48 a.m. | Last Modified: 18 Oct 2021, 10:48 a.m.
Panel Version: 2.222
Comment on publications: PMID:30269812 describes 2 unrelated consanguineous families (Saudi and Pakistani). Both have phenotype resembling Joubert syndrome (night blindness, rod-cone dystrophy, mild dysmorphic features, hypotonia (only in 1 family), ataxia, cerebellar vernis hypoplasia). Both are homozygous missense for the same amino acid residue (R149C, R149H). The authors performed some in vitro functional analysis.
PMID:16565502 describes a knockout mouse model of Arl3. The homozygous knockouts developed ciliary disease affecting kidney, biliary tract, pancreas and retina. However, there was no mention of a brain phenotype.
PMID:31743939 describes 2 large consanguineous Pakastani families with the same homozygous variant (Arg99Ile). There are 8 affected individuals in total and 7/8 had cone-rod dystrophy and no features of Joubert syndrome.
PMID:33748123 describes a Chinese family. Proband is compound het (c.91A>G, p.T31A; c.353G>T, p.C118F) and has retinal dystrophy. Heterozygous father has late onset and mild rode-cone dystrophy. Mother and sister (het) are normal. All family members did not have any other phenotypes.
PMID:26964041 describes a family with affected mother, son and daughter with retinitis pigmentosa. Affected patients were heterozygosity for Y90C. The mother's parents do not have the variant suggesting that it is a de novo event in the mother. No functional studies of the variant were performed.
PMID:30932721 reports a case where a patient has a de novo Y90C variant and has RP.
PMID:34485303 reports a heterozygous Asp67Val variant segregating in an Ashkenazi Jewish family with a dominant inherited retinal degenerations.
Created: 18 Oct 2021, 10:46 a.m. | Last Modified: 18 Oct 2021, 10:46 a.m.
Panel Version: 2.220
Submitted on behalf of the GMS Eye specialist group. These genes are also from RetNet. There is currently not enough evidence to rate these genes Green, therefore they have been given an Amber rating.
Created: 27 Dec 2019, 9:10 a.m. | Last Modified: 27 Dec 2019, 9:10 a.m.
Panel Version: 2.5
Tag Q4_21_rating was removed from gene: ARL3.
Source Expert Review Green was added to ARL3. Rating Changed from Amber List (moderate evidence) to Green List (high evidence)
Tag Q4_21_rating tag was added to gene: ARL3.
Mode of inheritance for gene: ARL3 was changed from to BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Phenotypes for gene: ARL3 were changed from to Joubert syndrome 35, OMIM:61816; cone-rod dystrophy, MONDO:0015993; Retinitis pigmentosa 83, OMIM:618173
Publications for gene: ARL3 were set to
gene: ARL3 was added gene: ARL3 was added to Retinal disorders. Sources: Expert Review Amber,RetNet,NHS GMS Mode of inheritance for gene: ARL3 was set to