Blanton et al. (1991) described a large extended American family (UCLA-RP01) segregating autosomal dominant retinitis pigmentosa with relatively late onset of night blindness, usually by the third decade of life, and with slow progression. Characteristic clinical findings included ... Blanton et al. (1991) described a large extended American family (UCLA-RP01) segregating autosomal dominant retinitis pigmentosa with relatively late onset of night blindness, usually by the third decade of life, and with slow progression. Characteristic clinical findings included diffuse retinal pigmentation, progressive decrease in recordable ERGs, and concentric visual field loss. Funduscopic findings included retinal atrophy, bone-spicule-like pigment deposits, and vascular attenuation. The UCLA-RP01 family had previously been reported by Heckenlively et al. (1982) and Daiger et al. (1989). All of those affected could trace their disease to an affected ancestor living in the early 19th century.
Pierce et al. (1999) identified a photoreceptor-specific gene (called RP1 or ORP1 for 'oxygen-regulated photoreceptor protein-1'; 603937) in the same interval on 8q11-q13 to which RP1 had been mapped by Xu et al. (1996). The expression of the ... Pierce et al. (1999) identified a photoreceptor-specific gene (called RP1 or ORP1 for 'oxygen-regulated photoreceptor protein-1'; 603937) in the same interval on 8q11-q13 to which RP1 had been mapped by Xu et al. (1996). The expression of the gene was modulated by retinal oxygen levels in vivo. In affected members of the UCLA-RP01 family studied by Blanton et al. (1991) and others, Pierce et al. (1999) identified heterozygosity for a nonsense mutation in the RP1 gene (R677X; 603937.0001). Pierce et al. (1999) stated that the R677X mutation was present in approximately 3% of cases of dominant RP in North America. Pierce et al. (1999) also detected 2 deletion mutations that caused frameshifts and introduced premature termination codons in 3 other families with dominant RP (603937.0002 and 603937.0003). Thus, the data suggested that mutations in this gene cause dominant RP, and that the encoded protein has an important but unknown role in photoreceptor biology. Sullivan et al. (1999) likewise isolated the RP1 gene and identified mutations in affected families, including the R677X mutation in the UCLA-RP01 family as well as the Australian family (family D) previously studied by Xu et al. (1996), and a different nonsense mutation in the British family (UK-RP1) originally reported by Inglehearn et al. (1999) (Q679X; 603937.0004). They found that the 2 severely affected members of the UCLA-RP01 family were homozygous for RP1 mutations: 1 had noticeable night blindness at age 6, visual field loss by 8, and severe retinal atrophy and nonrecordable ERGs by age 18. Her youngest brother, examined at age 7, had experienced night blindness since early childhood and already had severe visual field constriction. To determine the frequency and range of mutations in RP1, Bowne et al. (1999) screened probands from 56 large adRP families for mutations in the entire gene. After preliminary results indicated that mutations seemed to cluster in a 442-nucleotide segment of exon 4, an additional 194 probands with adRP and 409 probands with other degenerative retinal diseases were tested for mutations in this region alone. Bowne et al. (1999) identified 8 different disease-causing mutations, 6 of which were novel, in 17 of the 250 adRP probands tested. All of these mutations were either nonsense or frameshift mutations and led to severely truncated proteins. Based on this study, Bowne et al. (1999) estimated that mutations in RP1 cause at least 7% of adRP and that the 5-bp deletion (603937.0002) and the R677X mutation account for 59% of these mutations. In all affected members of a large family segregating adRP linked to the RP1 locus (Iannaccone et al., 1996), Guillonneau et al. (1999) identified the R677X mutation (603937.0001); the mutation was absent in unaffected members and in 100 unrelated controls. In affected members of 2 consanguineous Pakistani families with RP, Khaliq et al. (2005) identified homozygosity for a missense mutation in the RP1 gene (603937.0006). In affected members of another consanguineous Pakistani family with RP, they identified homozygosity for a 4-bp insertion in RP1 (603937.0007). Audo et al. (2012) studied a French cohort consisting of 114 patients with autosomal dominant RP and found a prevalence of RP1 mutations of 5.3%, similar to the prevalence reported in other cohorts from the United States and the United Kingdom. Audo et al. (2012) stated that variable penetrance of the disease was observed in their cohort as well as in others, and that most patients with RP1 mutations show classic signs of RP with relatively preserved central vision and visual fields.