Retinal disorders

Gene: PAX6

I don't know

Comment on list classification: There are multiple families reported with foveal hypoplasia and with monoallelic PAX6 variants. However, expert opinion is sought from the NHS Genomic Laboratory Hubs on whether the foveal hypoplasia phenotype fits within the scope of the retinal disorders panel.

Created: 4 Nov 2025, 12:17 p.m. | Last Modified: 4 Nov 2025, 12:17 p.m.

Panel Version: 8.59

Comment on phenotypes: OMIM phenotypes accessed on 04 November 2025.

Created: 4 Nov 2025, 10:30 a.m. | Last Modified: 4 Nov 2025, 10:30 a.m.

Panel Version: 8.58

Green review from Mohammed Derar suggests that there are multiple families with isolated foveal hypoplasia and without aniridia having monoallelic variants in PAX6. However, previous review suggests that this gene was kept red after discussion with Gavin Arno (an NHS expert) as PAX6 is a developmental eye disease gene and phenotype manifests as foveal hypoplasia, which while not a retinal dystrophy, only apparent in the posterior segment in some cases.

Created: 12 Nov 2024, 6:42 p.m. | Last Modified: 12 Nov 2024, 6:42 p.m.

Panel Version: 7.1

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Foveal hypoplasia 1, OMIM:136520; Microphthalmia/coloboma 12, OMIM:120200; ?Coloboma of optic nerve, OMIM:120430; ?Morning glory disc anomaly, OMIM:120430; Aniridia, OMIM:106210; Cataract with late-onset corneal dystrophy, OMIM:106210; Keratitis, OMIM:148190; Optic nerve hypoplasia, OMIM:165550; Anterior segment dysgenesis 5, multiple subtypes, OMIM:604229

Red List (low evidence)

GEL curator acknowledge conflicting ratings, Gavin Arno comments still stands as NHS expert. Will reassess if required

Created: 25 May 2022, 9:59 a.m. | Last Modified: 25 May 2022, 9:59 a.m.

Panel Version: 2.271

Green List (high evidence)

Additional evidence from multiple families with isolated foveal hypoplasia (without aniridia) having monoallelic variants in PAX6.

Created: 2 Jul 2024, 3:25 p.m. | Last Modified: 2 Jul 2024, 5:21 p.m.

Panel Version: 5.15

Monoallelic PAX6 variants are typically associated with aniridia and anterior segment abnormalities with foveal hypoplasia being part of the clinical spectrum. However, monoallelic missense variants in PAX6 are reported to cause isolated foveal hypoplasia which is autosomal dominant (Hingorani et al., 2009; Thomas et al., 2014).

Created: 7 Mar 2022, 4:18 p.m. | Last Modified: 7 Mar 2022, 4:18 p.m.

Panel Version: 2.242

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown

Phenotypes
foveal hypoplasia; optic nerve hypoplasia; anirdia

Publications

• (Hingorani et al., 2009) (PMID: 19218613)
• (Thomas et al., 2014) (PMID: 23942204)
• (Cunha et al., 2021) (PMID: 33024313)
• (Jiang et al., 2021) (PMID:34415986)
• (Azuma et al., 1996) (https://doi.org/10.1086/302529)

Red List (low evidence)

PAX6 is kept as a red gene after discussion and advise from Gavin Arno (UCL Institute of Ophthalmology/Moorfields Eye Hospital): “PAX6 is a developmental eye disease gene - this can manifest as foveal hypoplasia, which while not a retinal dystrophy, PAX6 may only be apparent in the posterior segment in some cases. Perhaps best left off the retina panel.”

Created: 30 Aug 2019, 2:43 p.m. | Last Modified: 30 Aug 2019, 2:43 p.m.

Panel Version: 1.159

Green List (high evidence)