Next Generation Sequencing in Pigmented Paravenous Retinochoroidal Atrophy

Abstract

Purpose : Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare disease characterized by bilateral symmetric paravenous retinochoroidal degeneration with accumulation of pigment clumps. The underlying cause for PPRCA remains unknown, but genetic etiology and secondary infectious or inflammatory processes have been proposed. In this study, we conducted a case review of genetic test results in patients with PPRCA.

Methods : This is a retrospective observational case study, wherein all electronic medical records with a previous diagnosis of PPRCA at Casey Eye Institute underwent review of the chart and fundus photography. Of the 19 identified records, 9 patients had characteristic fundus findings consistent with PPRCA with no evidence of secondary uveitic etiology. Of these patients, 5 had large panel genetic testing using next generation sequencing (NGS) at one of our reference laboratories. The number of genes tested in the various NGS panels ranged from 183 to 260.

Results : Of the 9 patients with PPRCA, there were 3 males and 6 females. Two patients were siblings. The age at diagnosis ranged from 6 to 78 years (mean: 38 ±22 yrs). Average best-corrected visual acuity between the two eyes of each patient ranged from 20/15 to 20/80 (mean: 0.25 ±0.19 logMAR or 20/35). Three patients had negative results from genetic testing. One patient had one VUS in VCAN (c.4882G>A:p.Val1628Ile). One patient had one reported mutation in ABCA4 (p.Val2050Leu:c.6148G>C) and three VUS’s in ABCA4 (c.-92C>T), ROM1 (p.Arg229His:c.686G>A), and PITPNM3 (c.*88G>C), but notably had no characteristic fundus fleck deposits.

Conclusions : In this case series, patients with PPRCA were diagnosed over a wide age range, but presented with relatively preserved visual acuity. Large panel NGS was inconclusive in the five patients tested. Even though PPRCA has been associated with CRB1 in one reported family, CRB1 mutations were not identified in our cohort thus far. Future studies to expand genetic testing and utilize whole exome sequencing in larger cohorts will be necessary to further investigate the genetic etiology of PPRCA.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.