A novel mutation in RP1 is a major cause of autosomal dominant retinitis pigmentosa in Southern Italy.

Background: To date, 22 different genes have been associated to autosomal dominant retinitis pigmentosa (ADRP), but they account for only 50% of cases worldwide. Methods: We analyzed by DHPLC and sequencing the major ADRP genes, namely, rhodopsin (RHO), peripherin 2 (PRPH2), retinitis pigmentosa 1 (RP1) and con-rod homeobox containing gene (CRX), in 130 Italian families affected by ADRP. To expand our data, we analyzed by DNA sequence capture and next-generation sequencing 260 genes associated to inherited eye diseases in three ADRP patients without mutations in RHO, RP1, RDS and CRX. Results: In 17 of the studied ADRP families (13%), we identified eleven different potentially pathogenic mutations. In our ADRP patients, the relative involvement of RHO (<7.5%) and PRPH2 (<1%) is lower than in US and UK. In contrast, about 6% of our patients have mutations in RP1. Surprisingly, a single, novel, nonsense mutation in RP1 (p.S740X) accounts for more than 4% of our cases and therefore can be considered a major cause of ADRP at least in Southern Italy. The next generation sequencing screening allowed the identification of possibly pathogenic variations in all the three analyzed patients. Conclusions: Despite the evident wide genetic heterogeneity in Italian patients, our data suggest that priority should be given to the analysis of RHO and RP1. Moreover, our extended analysis strongly indicates that advanced, high-throughput technologies for molecular screening of ADRP-associated genes are warranted for speed and cost-effective reasons.