Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by a progressive degeneration of photoreceptors, eventually resulting in severe visual impairment.
For a discussion of genetic heterogeneity of RP, see 268000. ... Retinitis pigmentosa (RP) is a clinically and genetically heterogeneous group of retinal dystrophies characterized by a progressive degeneration of photoreceptors, eventually resulting in severe visual impairment. For a discussion of genetic heterogeneity of RP, see 268000.
Al-Maghtheh et al. (1998) found a missense change (arg659 to ser) in the PRKCG gene (176980) in 2 families with RP11-linked dominant RP. The PRKCG gene encodes a form of protein kinase C that is expressed in the ... Al-Maghtheh et al. (1998) found a missense change (arg659 to ser) in the PRKCG gene (176980) in 2 families with RP11-linked dominant RP. The PRKCG gene encodes a form of protein kinase C that is expressed in the retina. Only 1 of the 2 families clearly exhibited the hallmark characteristic of RP11, namely asymptomatic, obligate carriers who transmitted the disease to offspring. Al-Maghtheh et al. (1998) failed to discover a mutation in PRKCG in 3 other families with reduced penetrance showing linkage to this region. Dryja et al. (1999) found no mutations in PRKCG in 3 families that showed linkage to 19q, where both RP11 and PRKCG map, and the characteristic reduced penetrance of RP11. Vithana et al. (2001) stated that the PRKCG gene is not involved in RP11. Vithana et al. (2001) identified mutations in the PRPF31 gene in families and individuals with RP11. The mutations included missense substitutions, deletions, and insertions (606419.0001-606419.0007). The type of incomplete penetrance demonstrated by mutations of the RP11 locus has been described as 'all or none,' where gene carriers display either fully symptomatic phenotype or completely asymptomatic phenotype (Al-Maghtheh et al., 1994, Al-Maghtheh et al., 1996, McGee et al., 1997). Wang et al. (2003) described a Chinese kindred with high penetrance of retinitis pigmentosa in association with a 12-bp deletion of PRPF31 (606419.0008). Waseem et al. (2007) noted that RP11 only results from coinheritance of a mutated allele and a wildtype low-expressed allele. They suggested that a high prevalence of low-expressing alleles in certain populations may account for the PRPF31 mutations being identified in patients with RP11 with apparent complete penetrance. Waseem et al. (2007) identified 6 PRPF31 mutations, 4 of which were novel, in a cohort of 118 patients with autosomal dominant RP in the U.K. The age of onset and the severity of the disease varied with different mutations, and individuals carrying the same mutation showed a range of phenotypic variation, suggesting the involvement of other modifying genes. In a previously reported family segregating autosomal dominant RP with reduced penetrance (Berson et al., 1969; McGee et al., 1997), in which extensive screening had failed to detect a PRPF31 mutation (McGee et al., 2002; Rivolta et al., 2006), Rio Frio et al. (2009) sequenced the entire PRPF31 genomic region using the Sanger method and ultrahigh-throughput analysis and identified a splice site mutation (606419.0009) that was common to all patients and obligate asymptomatic carriers and was not found in 300 control chromosomes.