Retinitis pigmentosa is characterized by constriction of the visual fields, night blindness, and fundus changes, including 'bone corpuscle' lumps of pigment. RP unassociated with other abnormalities is inherited most frequently (84%) as an autosomal recessive, next as an ... Retinitis pigmentosa is characterized by constriction of the visual fields, night blindness, and fundus changes, including 'bone corpuscle' lumps of pigment. RP unassociated with other abnormalities is inherited most frequently (84%) as an autosomal recessive, next as an autosomal dominant (10%), and least frequently (6%) as an X-linked recessive in the white U.S. population (Boughman et al., 1980). For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
The X-linked form of retinitis pigmentosa is also called choroidoretinal degeneration, or pigmentary retinopathy. The gyrate choroidal atrophy described by Waardenburg (1932) as X-linked was found on further study to be retinitis pigmentosa (Waardenburg et al., 1961). As ... The X-linked form of retinitis pigmentosa is also called choroidoretinal degeneration, or pigmentary retinopathy. The gyrate choroidal atrophy described by Waardenburg (1932) as X-linked was found on further study to be retinitis pigmentosa (Waardenburg et al., 1961). As pointed out in a review by Jacobson and Stephens (1962), there are some phenotypic differences between reported families. The genetic significance of these differences is unknown. There may be a fully recessive and an intermediate X-linked form. Affected males show typical 'bone corpuscle' clumps of pigment on funduscopic examination and progressive choroidal sclerosis leading to complete blindness. Hoare (1965) described a choroidoretinal disorder in 10 males in 7 sibships who were offspring of sisters. The maternal grandfather of the affected males was probably also affected. The condition was detected in childhood. Some carrier women showed fundus abnormalities with visual impairment beginning in middle age and probably showing progression. The condition in males resembled retinitis pigmentosa in fundus picture and night blindness, but differed by the absence of annular scotoma, by early involvement of central vision, and by relatively little vascular change. In fact, many males with RP2 show choroidoretinal atrophy in the advanced stages (Bird, 1975). In 21 females heterozygous for X-linked RP (XLRP), Ernst et al. (1981) found reduced flicker sensitivity over the whole frequency range where thresholds could be tested. Bundey and Crews (1986) concluded that the likelihood of an isolated male with severe retinitis pigmentosa having the X-linked form is about 1 in 2; of 74 male index patients, 21 had X-linked disease. In the family reported by Heck (1963), some heterozygous females were fully affected and some showed only a blue-yellow color defect (a rare anomaly). 'Tapetal reflex' was not present. The type of retinal degeneration was variable, being pigmentary, nonpigmentary, or macular in different affected males. Cataract was present in 2 with pigmentary degeneration. Fishman et al. (1988) profiled the clinical findings in 56 patients with X-linked retinitis pigmentosa from 35 families. Ultrastructural observations suggested that the rod photoreceptors are severely affected by the mutation in this disorder. Because photoreceptors develop from ciliated progenitors, it has been suggested that the axoneme may play a role in the development of photoreceptors. For this reason, Hunter et al. (1988) studied sperm axoneme structure in 8 patients with X-linked retinitis pigmentosa. A significant increase in the percentage of abnormal sperm tails was observed. Similar observations have been reported in Usher syndrome (276900). Kaplan et al. (1990) suggested that phenotypically there are 2 forms of X-linked RP: one form has very early onset with severe myopia (mean age of onset = 3.5 years; 1 SD = 0.05); the other form starts later with night blindness with or without mild myopia (mean age of onset = 10.6 years; 1 SD = 4.1). Kaplan et al. (1992) presented linkage evidence that the clinical form with early myopia as the initial symptom is associated with the RP2 gene, while the clinical form with later night blindness as the initial symptom is associated with the RP3 gene. Friedrich et al. (1993) found on reexamination of 7 obligate carrier females and 6 daughters of obligate carriers whose linkage relationships suggested that they carried the RP2 gene that the phenotype varied from totally normal eyes through mild retinal changes to complete loss of vision. Grover et al. (2000) evaluated the progression of visual impairment in carriers of X-linked recessive retinitis pigmentosa. They described the relationship between retinal findings at presentation and the extent of subsequent deterioration. They followed visual acuity, visual field, and electroretinograms in 27 carriers of XLRP and described 4 grades of fundus findings from grade 0 (normal) to grade 3 (diffuse changes). They found that carriers of XLRP with only a tapetal-like retinal reflex (grade 1) at presentation were more likely to retain visual function than those with peripheral retinal pigmentation. Grover et al. (2000) concluded that these data are useful in counseling such carriers as to their visual prognosis. Grover et al. (2002) compared the extent of intraocular light scatter (straylight) in carriers of choroideremia (CHM; 303100) and the various forms of XLRP to clarify the relationship between photoreceptor cell degeneration and intraocular light scatter in hereditary retinal degenerations. The carriers of XLRP who had evidence of photoreceptor cell dysfunction (as determined by visual field loss and reduced electroretinogram amplitudes) had increased levels of intraocular straylight, whereas the carriers of CHM, who showed fundus abnormalities alone, in the absence of demonstrable photoreceptor cell dysfunction, had normal or minimally elevated levels of light scatter. The authors concluded that the clinical symptom of glare, often reported by patients with RP, results, at least in part, from increased intraocular straylight caused by alterations in the optical quality of the crystalline lens as a consequence of photoreceptor cell degeneration.
In 6 patients with X-linked retinitis pigmentosa, Schwahn et al. (1998) detected 6 different mutations in a novel gene (RP2; 300757).
In a cohort of North American families with X-linked retinitis pigmentosa, Mears et al. (1999) ... In 6 patients with X-linked retinitis pigmentosa, Schwahn et al. (1998) detected 6 different mutations in a novel gene (RP2; 300757). In a cohort of North American families with X-linked retinitis pigmentosa, Mears et al. (1999) reported 5 protein truncation mutations of the RP2 gene. These were different from the 7 reported in European families by Schwahn et al. (1998), suggesting a high rate of new mutations and a lack of founder effect. Chapple et al. (2000) identified putative sites for N-terminal acyl modification by myristoylation and palmitoylation in the RP2 protein, consistent with its primary localization in the plasma membrane in cultured cells. Mutations in residues potentially required for N-terminal acylation revealed that the palmitoyl moiety is responsible for targeting of the myristoylated protein from intracellular membranes to the plasma membrane. The ser6del mutation (300757.0001) interfered with targeting of the protein to the plasma membrane, suggesting to the authors that the ser6del mutation may cause XLRP because it prevents normal amounts of RP2 from reaching the correct cellular locale. The R118H mutation (300757.0003) did not have a similar effect on localization. Miano et al. (2001) identified 5 novel mutations in RP2, each in a different XLRP family. These mutations included 3 missense mutations, a splice site mutation, and a single base insertion, which, because of a frameshift, led to a premature stop codon. Grayson et al. (2002) examined the relationship between RP2, cofactor C (602971), and ARL3 (604695) in patient-derived cell lines and in the retina. Examination of lymphoblastoid cells from patients with the arg120-to-ter mutation in RP2 (R120X; 300757.0008) revealed that the expression levels of cofactor C and ARL3 were not affected by the absence of RP2.