Retinitis Pigmentosa 31
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-31 (RP31) is caused by heterozygous mutation in the gene encoding topoisomerase I-binding arginine/serine-rich protein (TOPORS; 609507) on chromosome 9p21.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.Clinical Features
Papaioannou et al. (2005) examined 14 members of a French Canadian family segregating early-onset retinitis pigmentosa in an autosomal dominant fashion. Onset of symptoms ranged from 10 to 50 years of age and differed between the generations. Visual acuities were well maintained in most patients, with 13 of 14 having better than 20/40 and 9 of 14 having 20/20 acuities at their last examination. Visual field sizes ranged from 10 to 80 degrees, and electroretinogram (ERG) abnormalities were highly variable as well, with early rod defects followed by cone defects. The earliest sign of disease, found in 3 children of the youngest generation, was an unusual perivascular cuff of retinal pigment epithelium atrophy surrounding the superior and inferior arcades. This progressed to a diffuse pigmentary retinopathy with choroidal sclerosis. One of the patients with a completely normal retinal appearance had ERG abnormalities similar to the symptomatic patients.Mapping
In a French Canadian family with early-onset autosomal dominant retinitis pigmentosa, Papaioannou et al. (2005) excluded known loci and performed a genomewide search that established firm linkage (lod score = 6.3 at theta = 0.0) with a 31-cM region on chromosome 9p22-p13, flanked by markers D9S285 and D9S1874.Molecular Genetics
By sequencing genes located in the region of 9p21.1 identified as the critical region containing the RP31 gene, Chakarova et al. (2007) identified different heterozygous frameshift mutations in the TOPORS gene (609507) in 2 unrelated families with retinitis pigmentosa, including the family reported by Papaioannou et al. (2005). The lack of mutant TOPORS protein in patients was considered highly suggestive of haploinsufficiency, rather than a dominant-negative effect, as the molecular mechanism for disease, and made the clinical phenotype amenable to rescue by somatic gene therapy.