Punctiform and polychromatic pre-Descemet's corneal dystrophy: clinical evaluation and identification of the genetic basis

Session Details

Session Title: Cornea: Medical

Session Date/Time: Monday 16/09/2019 | 08:30-10:30

Paper Time: 09:18

Venue: Free Paper Forum: Podium 2

First Author: : J.Alio del Barrio SPAIN

Co Author(s): :    D. Chung   O. Al-Shymali   A. Aldave                       

Abstract Details

Purpose:

To define the corneal associations and genetic basis of punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD). This form of corneal dystrophy is currently considered a rare subtype of pre-Descemet corneal dystrophy (PDCD), and it has been given a poor level of evidence (category 4 according to the IC3D classification).

Setting:

Vissum Innovation and Universidad Miguel Hernández, Alicante, Spain. The Jules Stein Eye Institute, UCLA, Los Angeles, USA.

Methods:

Full ophthalmic assessment was performed for members of three unreported families with PPPCD. Whole-exome-sequencing (WES) was performed on the first family. Novel or rare variants that segregated with the affected status were screened for in the other two families with Sanger sequencing. Identified variants that segregated with the affected status in all families were characterized using in silico prediction tools and/or in vitro splice assays. Additionally, two previously reported PPPCD families (one of them with a rare form of PPPCD) were screened for variants identified in the three unreported PPPCD families.

Results:

Twelve of 21 examined members of the three unreported families were diagnosed with PPPCD. Affected individuals showed a significant increase in corneal hysteresis. Any other statistically significant corneal associations were found. WES and Sanger sequencing identified two variants that segregated with the affected status in the all three families: a rare intronic PDZD8 c.872+10A>T variant and a novel missense PRDX3 c.568G>C variant. Screening of two previously reported families identified the same PRDX3 variant in one family, the one expressing the typical PPPCD clinical phenotype. In silico prediction tools predicted the PRDX3 variant to be damaging the protein function.

Conclusions:

PPPCD increases corneal hysteresis and it is associated with a novel missense mutation in PRDX3 on chromosome 10. Screening of additional families will determine whether all families demonstrate a PRDX3 mutation, or whether locus heterogeneity exists. According to this finding, PPPCD should be considered a distinct inherited disorder and reclassified as a category 1 of evidence corneal dystrophy.

Financial Disclosure:

None