Novel rhodopsin mutations Gly114Val and Gln184Pro in dominant retinitis pigmentosa

To identify mutations in the rhodopsin gene in North American patients with autosomal dominant retinitis pigmentosa (ADRP) and to measure the proportion of cases with rhodopsin mutations.

Single-strand conformation polymorphism (SSCP) analysis and direct genomic sequencing were used to evaluate the coding region and intron splice sites of the rhodopsin gene for mutations in 91 unrelated patients.

Nineteen patients heterozygously carried a missense change in the rhodopsin gene (six with Pro23His, two with Pro347Leu, and one each with Thr17Met, Phe45Leu, Gly51Arg, Gly89Asp, Gly114Val, Arg135Trp, Pro171Leu, Gln184Pro, Phe220Leu, Ser297Arg, and Pro347Thr). All these missense changes were previously reported as causes for ADRP except for Gly114Val, Gln184Pro, and Phe220Leu, which were evaluated further by examining the relatives of index patients. The Gly114Val and Gln184Pro alleles cosegregated with ADRP as expected if they were pathogenic. Phe220Leu did not, indicating that it is not a cause of ADRP.

Summation of the results of cases in this study with those of 272 unrelated cases of ADRP previously evaluated by our group shows that 90 of 363 (25%) of cases were caused by rhodopsin mutations.