Retinitis Pigmentosa 70
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-70 (RP70) is caused by heterozygous mutation in the PRPF4 gene (607795) on chromosome 9q32.
For a general phenotypic description and discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical FeaturesChen et al. (2014) reported a 3-generation Chinese family segregating autosomal dominant retinitis pigmentosa (RP). The proband presented at age 15 years with poor night vision, and subsequently developed visual field (VF) restriction and impaired central vision. At age 58, he had bilateral cataracts and a typical RP fundus, exhibiting retinal degeneration with macular involvement, waxy pallor of the optic disc, narrowed vasculature, and peripheral pigment deposits. Optical coherence tomography revealed an attenuated outer nuclear layer and retinal pigment epithelium at the maculae with complete loss of the outer/inner segments, consistent with his poor visual acuity. Diffuse loss of VFs and diminished responses on electroretinography (ERG) were also observed. A sister and brother developed night blindness at 27 and 24 years of age, respectively, and at 66 and 47 years, they showed findings similar to those of the proband, including poor night vision, poor central visual acuity, severely reduced VFs, typical RP fundus appearance, and nearly undetectable ERG responses. Their deceased father was also reported to have been affected. Chen et al. (2014) also described a Chinese man who developed night blindness at 20 years of age, with constricted VFs and decreased visual acuity by 37 years. At age 53, he had severely impaired visual acuity, significantly restricted VFs, undetectable ERG responses, and a typical RP fundus.
Molecular GeneticsIn a 3-generation Chinese family segregating autosomal dominant retinitis pigmentosa (adRP), Chen et al. (2014) screened 179 retinal dystrophy-associated genes, including all known adRP genes, and 10 candidate genes involved with U4/U6-U5 tri-snRNP complex. They identified a heterozygous missense mutation in the PRPF4 gene (P315L; 607795.0001) in affected individuals, which was not present in unaffected family members, in 400 unrelated controls, or in SNP databases. Sequencing the PRPF4 gene in another 225 Chinese RP probands revealed an 18-bp deletion (607795.0002) in a sporadic RP patient.
In 402 probands with adRP, including 191 from North America who were negative for mutation in 90% of known adRP genes, 115 from Spain who were negative for known RP mutations, and 96 from France who were negative for mutation in the 10 most frequently mutated RP genes or hotspots, Benaglio et al. (2014) analyzed the PRPF4 gene but did not find any clearly pathogenic mutations. Noting that mutations in PRPF4 had been identified as a cause of adRP in Chinese patients, the authors suggested that there might be a population-specific effect.