Retinitis Pigmentosa 44
A number sign (#) is used with this entry because this form of retinitis pigmentosa is caused by homozygous or heterozygous mutation in the gene encoding the RPE-retinal G protein-coupled receptor (RGR; 600342) on chromosome 10q23.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical FeaturesUsing a single-strand conformation technique, Morimura et al. (1999) searched for mutations in the exons and flanking intron sequences of RGR in 182 unrelated patients with dominantly inherited retinitis pigmentosa, 182 with recessive retinitis pigmentosa, 383 with simplex retinitis pigmentosa (sporadic cases), 45 with Leber congenital amaurosis (see 204000), 28 with retinitis punctata albescens (see 136880), 22 with choroidal sclerosis (see 303100), and approximately 95 normal controls. They identified 2 probands with mutations in the RGR gene. One proband with autosomal recessive RP had 4 affected sibs. All affected sibs (aged 35 to 44) had visual acuity of 20/200 or worse, severely constricted visual fields, attenuated retinal vessels, diffuse depigmentation of the retinal pigment epithelium (RPE), and intraretinal pigment deposits in the periphery. The depigmented patches involved the central macula in those sibs with severely decreased acuity. Full-field electroretinograms (ERGs) from 2 sibs were reduced, reflecting widespread loss of photoreceptor function. The other proband, who was found to have 2 affected sibs, had retinal degeneration comparable to that of patients from the first family. This patient, who had originally been diagnosed with choroidal sclerosis (see 215500), had poor visual acuity and severely reduced ERGs that were nevertheless larger than those of patients up to 30 years younger from the first family. The deceased father of this proband was said to have been affected, making it likely that the retinal degeneration in this family is dominantly inherited.
Molecular GeneticsIn affected members of families with autosomal recessive and autosomal dominant RP, Morimura et al. (1999) detected homozygous and heterozygous mutations, respectively, in the RGR gene. The 5 affected sibs with autosomal recessive inheritance carried a missense mutation (S66R; 600342.0001); the 3 affected sibs with autosomal dominant inheritance, a 1-bp insertion (600342.0002).
Using D-HPLC and direct sequencing, Ksantini et al. (2010) analyzed the RGR gene in 134 patients with autosomal recessive or sporadic RP, 79 cases with autosomal dominant RP, 36 RP cases with undetermined inheritance, and 113 patients with other retinal dystrophies, but did not find any pathogenic mutations. The authors concluded that mutations in RGR occur rarely in inherited retinal dystrophies.