CONCOMITANT MUTATIONS IN INHERITED RETINAL DYSTROPHIES: Why the Reproductive and Therapeutic Counseling Should Be...

To highlight the challenge of correct reproductive and therapeutic counseling in complex pedigrees with different inherited retinal dystrophies (IRD).

Two hundred eight patients diagnosed with nonsyndromic IRD underwent full ophthalmologic examination and molecular analysis using targeted next-generation sequencing.

Five families (4%) carried mutations in more than one gene that contribute to different IRD. Family fRPN-NB had a dominant mutation in SNRNP200, which was present in nine affected individuals and four unaffected, and a mutation in RP2 among 11 family members. Family fRPN-142 carried a mutation in RPGR that cosegregated with the disease in all affected individuals. In addition, the proband also harbored two disease-causing mutations in the genes BEST1 and SNRNP200. Family fRPN-169 beared compound heterozygous mutations in USH2A and a dominant mutation in RP1. Genetic testing of fRPN-194 determined compound heterozygous mutations in CNGA3 and a dominant mutation in PRPF8 only in the proband. Finally, fRPN-219 carried compound heterozygous mutations in the genes ABCA4 and TYR.

These findings reinforce the complexity of IRD and underscore the need for the combination of high-throughput genetic testing and clinical characterization. Because of these features, the reproductive and therapeutic counseling for IRD must be approached with caution.