Punctiform and polychromatic pre-Descemet's dominant corneal dystrophy: report of two independent families, clinical findings, and the results of whole exome sequencing

Session Details

Session Title: Cornea Miscellaneous

Session Date/Time: Monday 24/09/2018 | 16:30-18:00

Paper Time: 16:48

Venue: Room A3, Podium 3

First Author: : J.Alió del Barrio SPAIN

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

Abstract Details

Purpose:

To report the clinical features and genetic basis of two previously unreported families with punctiform and polychromatic pre-Descemet corneal dystrophy (PPPCD).

Setting:

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

Methods:

Eight of the 13 family members from Family-1 and three of the six family members from Family-2 were diagnosed with PPPCD based on the presence of polychromatic posterior stromal opacities by clinical examination, specular and confocal microscopy. Family-1: DNA was collected from 10 family members for whole exome sequencing (WES). Alignment, variant calling and annotation were performed using commercially available software programs. PPPCD related gene was then verified by DNA collection and WES of 5 family members from Family-2. Full clinical examination was performed in all patients: topography, visual function, refraction, corneal and ocular aberrometry, scattering index and corneal hysteresis.

Results:

No novel or rare (MAF <0.5%) non-synonymous or splice-site coding variants were identified in all 6 affected family-1 members and none of the unaffected family-1 members. Two non-coding variants were identified that segregated with the affected phenotype in the family-1 members that underwent WES, one of which also segregated in the family members that did not undergo WES, and is expressed in keratocytes and corneal endothelial cells. DNA analysis from family-2 will be presented. No significant differences were observed in any of the clinical findings (affected patients were different only by the expression of polychromatic preDescemetic opacities).

Conclusions:

We report only the 9th and 10th family with PPPCD in the literature. Through the use of WES, we have identified a candidate gene for PPPCD, and we are currently analyzing the family-2 DNA to investigate the potential role of this gene in PPPCD further. This finding would confirm, for the first time, the genetic basis and autosomal dominant inheritance of this rare form of corneal dystrophy. PPPCD is currently considered a subtype of Pre-Descemet Corneal Dystrophy (PDCD) with a category 3 of evidence, but these findings suggest that PPCD should be considered as an independent entity with category 1.

Financial Disclosure:

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