ClinVar Genomic variation as it relates to human health

In a patient with retinitis pigmentosa (RP1; 180100), Pierce et al. (1999) found a C-to-T transition in exon 4 of the RP1 gene, resulting in a nonsense mutation, CGA (arg) to TGA (ter). This mutant allele, if expressed, would encode a protein of 676 amino acids, 1,480 less than the predicted wildtype RP1 protein. The mutation was first identified in the family in which Blanton et al. (1991) identified linkage to chromosome 8. The first member of the family studied was the offspring of 2 affected parents who were distantly related and presumed to carry the same RP1 mutation. The patient was found to be homozygous for the R677X mutation as was one of her sibs. Analysis of codon 677 in 17 other family members revealed that all of these affected members were heterozygotes. This family was also studied by Sullivan et al. (1999), who reported that the homozygotes were unusually severely affected. Pierce et al. (1999) evaluated 242 patients with autosomal dominant RP from separate families across the United States and Canada for the R677X mutation. Patients with known mutations in other dominant RP genes, RHO (180380) or RDS (PRPH2; 179605), were excluded from this analysis. They found 10 patients who were heterozygous for the R677X mutation. All 10 patients, who were examined at an age ranging from 35 to 49 years, with the mean age being 41.7 years, had findings typical of retinitis pigmentosa: night blindness as an early symptom, constricted visual fields, and funduscopic findings of attenuated vessels and intraretinal pigmentation. Pierce et al. (1999) reported that this mutation was present in approximately 3% of cases of autosomal dominant retinitis pigmentosa in North America. In affected members of an Australian RP1 family (family D), previously studied by Xu et al. (1996), Sullivan et al. (1999) identified heterozygosity for the same R677X mutation in the RP1 gene as had been found in the UCLA-RP01 family. Sullivan et al. (1999) noted that 2 distinct haplotypes segregated with disease in the 2 families, suggesting that the families were not related or that the mutation was very old. In a family with autosomal dominant retinitis pigmentosa reported by Iannaccone et al. (1996) to be linked to 8q, Guillonneau et al. (1999) identified the R677X mutation in the RP1 gene. (less)