Oh et al. (2000) reported the clinical characteristics of a family with autosomal dominant retinitis pigmentosa caused by a pro23-to-ala mutation (P23A; 180380.0043) in the rhodopsin gene, and compared this phenotype with that associated with the more common ... Oh et al. (2000) reported the clinical characteristics of a family with autosomal dominant retinitis pigmentosa caused by a pro23-to-ala mutation (P23A; 180380.0043) in the rhodopsin gene, and compared this phenotype with that associated with the more common pro23-to-his mutation (P23H; 180380.0001). The rare P23A mutation caused a mild RP in presentation and course, with greater preservation of ERG amplitudes than that resulting from the more prevalent P23H mutation. Jacobson et al. (1991) studied rod and cone function in 20 patients from 6 families with autosomal dominant RP due to 5 different point mutations in the rhodopsin gene. In addition to traditional ocular examination methods and electroretinography, they performed dark- and light-adapted perimetry, dark adaptometry, and imaging fundus reflectometry. Jacobson et al. (1991) observed discernible differences in the pattern of retinal dysfunction between families with different mutations (see T58R, 180380.0004; T17M, 180380.0006; and Q344X, 180380.0015) and noted that 3 families with mutations at the same amino acid position, arg135 (see R135W, 180380.0012, and R135L, 180380.0011), showed a similar functional phenotype involving early, severe retinal dysfunction with no intrafamilial variability. Andreasson et al. (1992) reported a 6-generation Swedish family segregating autosomal dominant retinitis pigmentosa in whom they identified an R135L mutation (180380.0011). They noted that affected members of this family had a history of night blindness from early childhood and visual field losses were always noted before age 20. Andreasson et al. (1992) concluded that the R135L mutation may cause a more rapidly progressive form of RP than other mutations. Pannarale et al. (1996) studied a large Sicilian pedigree with autosomal dominant retinitis pigmentosa due to the R135W mutation (180380.0012) in the rhodopsin molecule. The rate of progression of disease was unusually high, with an average 50% loss per year of baseline ERG amplitude and visual field area. Later in the course of the disease, macular function was also severely compromised, leaving only residual central vision by the fourth decade of life. Pannarale et al. (1996) concluded that the phenotype associated with mutations in codon 135 of the rhodopsin molecule appears to have an unusually high progression rate and to yield an extremely poor prognosis. Ponjavic et al. (1997) examined a 4-generation Swedish RP family with the R135W mutation, in whom they documented a severe form of RP similar to the phenotype observed by Andreasson et al. (1992) in a family with the R135L mutation. Ponjavic et al. (1997) noted that both mutations cause the substitution of hydrophobic amino acids at codon 135, and that point mutations in this specific region of the rhodopsin molecule seem to cause an aggressive form of retinitis pigmentosa. Sandberg et al. (2007) measured the rates of visual acuity, visual field, and electroretinogram (ERG) loss in 2 large cohorts, one of patients with XLRP (RP3; 300029) due to mutations in the RPGR gene (312610) and the other of patients with autosomal dominant RP due to mutations in the RHO gene. Patients with RPGR mutations lost Snellen visual acuity at more than twice the mean rate of patients with RHO mutations. The median age of legal blindness was 32 years younger in patients with RPGR mutation than in patients with RHO mutations. Legal blindness was due primarily to loss of visual acuity in RPGR patients and to loss of visual field in RHO patients. Using longitudinal data, Sakami et al. (2011) found that the earliest expression of retinal disease in ADRP patients with the P23H opsin mutation involved abnormal thinning of the outer nuclear layer and shortening of the rod outer segment. These changes were followed by shortening of the cone outer segment. With more extensive disease, there was further abnormality of inner and outer segments, followed by loss of all remaining photoreceptors.
In patients with autosomal dominant retinitis pigmentosa mapping to 3q, Dryja et al. (1990) identified a heterozygous pro23-to-his mutation (P23H; 180380.0001) in the RHO gene. The proline residue at position 23 in the NH2 portion of the rhodopsin ... In patients with autosomal dominant retinitis pigmentosa mapping to 3q, Dryja et al. (1990) identified a heterozygous pro23-to-his mutation (P23H; 180380.0001) in the RHO gene. The proline residue at position 23 in the NH2 portion of the rhodopsin gene is highly conserved. Dryja et al. (1990) reported 3 additional missense mutations (180380.0002-180380.0004) in the RHO gene in patients with RP4. They found that these 4 mutations accounted for 27 of 150 unrelated patients with ADRP (18%). In the original family with autosomal dominant retinitis pigmentosa linked to 3q (McWilliam et al., 1989), Farrar et al. (1992) demonstrated an arg207-to-met mutation (180380.0030) in the RHO gene. On the basis of a complete screen for mutations in the RHO gene in patients with autosomal dominant retinitis pigmentosa, Inglehearn et al. (1992) concluded that approximately 30% of such families have 'rhodopsin rp,' whereas the remainder probably have a defect elsewhere in the genome. Specifically they found 9 different RHO mutations in a total of 12 out of 39 families screened. Of those families in which rhodopsin mutations were found, 4 had the D type, 3 had the sectorial type, and the remainder were of uncertain classification. All families excluded from chromosome 3q by linkage had been classified R type. (The D ('diffuse') type, or type I ADRP, causes diffuse and severe loss of rod function with retention of cone function until much later in the disease process. Electroretinogram (ERG) and psychophysical testing show that rod function is abnormal over the entire fundus. The R-type disease causes 'regional' or patchy and equal loss of rod and cone function.) In a 5-generation Chinese Bai family segregating autosomal dominant RP, mapping to chromosome 3q, Guo et al. (2010) identified heterozygosity for the P347L mutation in the RHO gene (180380.0002). The authors stated that, although mutations in RHO account for approximately 7.7% of autosomal dominant RP in the Chinese Han population, this was the first RHO mutation reported in RP patients of the Chinese Bai nationality. In affected members of 2 Indonesian families segregating autosomal recessive RP4, Kartasasmita et al. (2011) identified a homozygous nonsense mutation in the RHO gene (180380.0045). Haplotype analysis suggested that this is a founder mutation.