Corneal dystrophy

Gene: PRDX3

I don't know

The 'founder-effect' tag has been added as the same variant has been identified in multiple families from the same ethnic background.

Created: 30 Sep 2025, 9:53 p.m. | Last Modified: 30 Sep 2025, 9:53 p.m.

Panel Version: 4.3

Comment on list classification: There are 5 cases with heterozygous variants in this gene and a corneal dystrophy phenotype. However, the same variant was found in all cases, and all had Spanish ancestry. WES was only performed in one family, with targetted sequencing in the others. Therefore rating Amber until further supporting evidence is reported, such as functional data, or cases with different ethnicities.

Created: 29 Sep 2025, 9:22 p.m. | Last Modified: 30 Sep 2025, 9:28 a.m.

Panel Version: 4.3

Associated with Corneal dystrophy, punctiform and polychromatic pre-Descemet in OMIM (OMIM:619871, AD).

There are 5 cases with the same rare heterozygous missense variant in PRDX3 and punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD) although the phenotype is variable. All cases are with Spanish ancestry and 3 of the cases were found to share the same mini-haplotype.

PMID: 31782998 (2020) - 3 previously unreported Spanish families with PPPCD were examined. Through WES and Sanger sequencing 3 heterozygous variants were found to segregate with the disease in family 1 (6 affected, 4 unaffected): PDZD8 c.872+10A>T, OR2M5 c.773T>C, and PRDX3 c.568.G>C. Sanger sequencing of the smaller families 2 and 3 found the same PDZD8 c.872+10A>T and PRDX3 c.568G>C, (p.Asp190His) variants in affected individuals but not the OR2M5 variants. PDZD8 c.872+10A>T was found to affect splicing. An additional 2 families were then examined for these variants - family 4 was found to carry the PRDX3 c.568.G>C variant. No variants in the 3 genes were found in family 5. The same mini-haplotype was identified in the three previously unreported families (PPPCD families 1, 2, and 3) but not in PPPCD family 4, suggesting that the PRDX3 c.568G>C variant likely arose from a common ancestor in PPPCD families 1–3 and independently in PPPCD family 4.
Affected individuals in families 1-4 presented with localization of opacities to the pre-Descemetic posterior stroma. In family 5, affected members presented an atypical PPPCD phenotype with opacities distributed through all levels of the corneal stroma. The authors conclude that since both PRDX3 c.568G>C and PDZD8 c.872+10A>T were identified in PPCD families 1–3 that likely share a common ancestor, but since the novel PRDX3 c.568G>C variant was also found in a fourth unrelated PPPCD pedigree, PRDX3 is likely the causative gene for PPPCD.

PMID: 34369396 (2022) 38 year old Spanish woman with bilateral polychromatic deposits diffusely distributed in the posterior stroma of each cornea, just anterior to Descemet membrane, as well as beneath the anterior lens capsule in each eye. Her father was also affected. Sequencing of PRDX3 and PDZD8 in the proband revealed the heterozygous PRDX3 c.568G>C variant but not the PDZD8 c.872+10A>T intronic variant.
Sources: Literature

Created: 29 Sep 2025, 9:19 p.m. | Last Modified: 30 Sep 2025, 9:27 a.m.

Panel Version: 4.3

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

Phenotypes
Corneal dystrophy, punctiform and polychromatic pre-Descemet, OMIM:619871; corneal dystrophy, punctiform and polychromatic pre-descemet, MONDO:0859248

Publications

• 31782998
• 34369396