Retinal disorders

Gene: JAG1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 26 Sep 2024, 3:50 p.m. | Last Modified: 26 Sep 2024, 3:50 p.m.

Panel Version: 6.7

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Green List (high evidence)

Comment on list classification: There is sufficient evidence available for the promotion of this gene to green rating in the next GMS review.

Created: 28 Feb 2024, 6:08 p.m. | Last Modified: 28 Feb 2024, 6:08 p.m.

Panel Version: 4.77

PMID:31273345 reported the identification of three novel rare variants in JAG1 gene (c.413C>T/ p.Ala138Val, c.1415G>A/ p.Arg472His, and c.2884A>G/ p.Thr962A) in three different families with familial exudative vitreoretinopathy. There is also functional data in support of this disease association.

PMID:34185059 reported from a retrospective, observational, multicenter, study on 23 subjects with Alagille syndrome that peripheral retinal abnormalities were the most frequent ocular finding, reported in 22 subjects (96%). JAG1 variants were found in 16 of these subjects, while one patient had no variant, four patients were not tested and molecular findings were not available in two patients.

Siying Lin (Moorfields Eye Hospital) reviewed that retinal findings were seen in at least 2 unrelated patients with Alagille syndrome within their inherited retinal dystrophy clinical cohort.

Created: 28 Feb 2024, 6:06 p.m. | Last Modified: 28 Feb 2024, 6:06 p.m.

Panel Version: 4.74

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Alagille syndrome 1, OMIM:118450; exudative vitreoretinopathy, MONDO:0019516

Publications

• 31273345
• 34185059

Green List (high evidence)

Well-demarcated peripheral chorioretinal atrophic changes appear to be a not infrequent finding in patiets with Alagille syndrome, and these retinal findings have also been seen in at least 2 unrelated patients with Alagille syndrome within our inherited retinal dystrophy clinical cohort

Created: 21 Feb 2024, 3:25 p.m. | Last Modified: 21 Feb 2024, 4:36 p.m.

Panel Version: 4.71

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Retinal dystrophy; peripheral chorioretial atrophy; Alagille syndrome

Publications

• PMID: 34185059

Mode of pathogenicity
Other

I don't know

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