Clinical characterization, linkage analysis, and PRPC8 mutation analysis of a family with autosomal dominant retinitis pigmentosa type 13 (RP13)

Abstract

A Dutch family with autosomal dominant retinitis pigmentosa (adRP) displayed a phenotype characterized by an early age of onset, a diffuse loss of rod and cone sensitivity, and constricted visual fields (type I). One male showed a mild progression of the disease. Linkage analysis showed cosegregation of the genetic defect with markers from chromosome 17p13.1-p13.3, a region overlapping the RP13 locus. The critical interval of the RP locus as defined in this family was flanked by D17S926 and D17S786, with a maximal lod score of 4.2 (theta = 0.00) for marker D17S1529. Soon after the mapping of the underlying defect to the 17p13 region, a missense mutation (6970G>A; R2310K) was identified in exon 42 of the splicing factor gene PRPC8 in one patient of this family. Diagnostic restriction enzyme digestion of exon 42 amplified from genomic DNA of all family members revealed that the R2310K mutation segregated fully with the disease. The type I phenotype observed in this family is similar to that described for three other RP13 families with mutations in PRPC8.