Next generation sequencing-based comprehensive molecular diagnosis of retinitis pigmentosa probands in Miami

Abstract

Purpose : Retinitis pigmentosa (RP) is a group of heterogeneous inherited retinal diseases, and the prevalence of RP and frequency of RP genotypes vary across populations. To examine if the mutation spectrum is distinct for patients with RP in the Miami area where a significant portion of the population is Hispanic, we performed targeted next-generation sequencing (NGS) for a cohort of unrelated RP cases recruited from the area.

Methods : Comprehensive molecular screening was performed using NGS approach targeting a panel of 186 known retinal human disease genes. Putative pathogenic mutations were identified and validated by Sanger sequencing. Segregation testing was conducted when additional family members are available.

Results : A total of 71 unrelated RP families were recruited, including 37 Hispanic families. Putative mutations (35 novel pathogenic mutations) were identified in 46 families, achieving a solving rate of 65%. In 9 families, the PRPF31 was mutant, making it the most commonly genotype. Mutations in other retinal disease genes (IMPG1, CDHR1) were observed in 2 families, providing potential new phenotype-genotype RP links.

Conclusions : To our knowledge, this was the first NGS comprehensive mutation screen for RP patients from the Miami area where a significant portion of the population is Hispanic. Distinct mutation spectrum has been observed with PRPF31 as the most common geneotype. A novel PRPF31 mutation was shared by three Cuba families, indicating a founder effect. Our results verified the genotype differences in populations and underscored the importance of a comprehensive, unbiased approach in clinical molecular diagnosis.

This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.