Retinal disorders

Gene: COL9A3

Green List (high evidence)

The rating of this gene has been updated to Green and the mode of inheritance set to 'BIALLELIC, autosomal or pseudoautosomal' following NHS Genomic Medicine Service approval.

Created: 6 Feb 2023, 8:21 a.m. | Last Modified: 6 Feb 2023, 8:21 a.m.

Panel Version: 3.30

There is sufficient evidence (>3 unrelated cases) linking this gene to retinal disorders (vitreoretinal degeneration, lattice degenerations, retinal pigmentary changes and recurrent rhegmatogenous retinal detachment) caused by autosomal recessive variants. However, these phenotypes overlap with that of Stickler syndrome and this gene is green on Stickler syndrome panel (https://panelapp.genomicsengland.co.uk/panels/3/gene/COL9A3/) This gene is also associated with Stickler syndrome in both OMIM and G2P.

PMID:33633367 reports two unrelated cases of peripheral vitreoretinal degeneration and retinal detachment caused by heterozygous variants in COL9A3 gene. However, as there are only two cases reported currently, we can only associate the gene with biallelic inheritance at the moment.

It has previously been decided (2019) in consultation with Gavin Arno (UCL Institute of Ophthalmology/Moorfields Eye Hospital) that other collagen genes associated with Stickler syndrome/ retinal phenotypes can stay red in this panel. Given this gene has recently been proposed for this panel by an expert, I am recommending that the Test Evaluation Working Group review and define the panel scope, and reach consensus as to whether this gene is appropriate for inclusion.

Created: 8 Jan 2023, 6:27 p.m. | Last Modified: 8 Jan 2023, 6:27 p.m.

Panel Version: 3.10

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Stickler syndrome, type VI, OMIM:620022

Publications

• 30450842
• 33570243
• 33633367

Review submitted on behalf of Robert Henderson, Mr Chien Wong, Mr CK Patel. Publications: Nash BM, Watson CJG, Hughes E, Hou AL, Loi TH, Bennetts B, Jelovic D, Polkinghorne PJ, Gorbatov M, Grigg JR, Vincent AL, Jamieson RV. Heterozygous COL9A3 variants cause severe peripheral vitreoretinal degeneration and retinal detachment. Eur J Hum Genet. 2021 May;29(5):881-886.Hanson-Kahn A, Li B, Cohn DH, Nickerson DA, Bamshad MJ; University of Washington Center for Mendelian Genomics, Hudgins L. Autosomal recessive Stickler syndrome resulting from a COL9A3 mutation. Am J Med Genet A. 2018 Dec;176(12):2887-2891.; Markova T, Sparber P, Borovikov A, Nagornova T, Dadali E. Clinical and genetic characterization of autosomal recessive stickler syndrome caused by novel compound heterozygous mutations in the COL9A3 gene. Mol Genet Genomic Med. 2021 Mar;9(3):e1620.

Created: 21 Dec 2022, 4:51 p.m. | Last Modified: 21 Dec 2022, 4:51 p.m.

Panel Version: 3.6

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
stickler syndrome; retinal degeneration, retinal detachment