Retinitis Pigmentosa 19
A number sign (#) is used with this entry because of evidence that retinitis pigmentosa-19 (RP19) can be caused by homozygous or compound heterozygous mutation in the ABCR gene (ABCA4; 601691) on chromosome 1p22.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical FeaturesIn the population of Spain, 39% of the retinitis pigmentosa pedigrees show an autosomal recessive pattern of inheritance (Ayuso et al., 1995). Martinez-Mir et al. (1997) described a consanguineous Spanish family in which 6 of 7 sibs were affected. The parents, who were related as second cousins, were unaffected. The mean age of onset was 8 years. Night blindness was followed by a decrease in visual acuity, starting at 14 years of age. Fundus examination showed papillary pallor, attenuated vessels, peripheral scattered pigmentation, bone spicule-like pigmentation reaching some areas of the macula, and severe atrophy of the retinal pigment epithelium.
MappingMartinez-Mir et al. (1997) demonstrated linkage (maximum lod = 3.64 at theta = 0.0) with marker D1S188 located at 1p21-p13, the same region as Stargardt disease (STGD1; 248200). Exhaustive ophthalmologic study of the patients clearly distinguished the disease from the Stargardt phenotype (and the fundus flavimaculatus phenotype, which is caused by mutations in the same gene) and revealed an atypical form of autosomal recessive RP with choroidal atrophy as a distinctive feature. Fluorescein angiography of individuals showing severe choriocapillaris atrophy were presented.
Molecular GeneticsSince RP19 maps to the same region of the short arm of chromosome 1 as the Stargardt disease locus, Martinez-Mir et al. (1998) sought mutations in the ABCR gene, which is mutant in Stargardt disease. They identified a 1847delA frameshift mutation in the ABCR gene (610691.0008) in a consanguineous Spanish family that showed linkage to 1p.
In a family segregating RP19 and STGD1 in 2 first cousins, Rozet et al. (1999) found that heterozygosity for a splice acceptor site mutation in the ABCR gene (601691.0017) resulted in STGD1, whereas hemizygosity for this mutation resulted in RP19. In the patient with RP19, a partial deletion of the maternal ABCR gene was presumed to be the source of a null allele, although this was not conclusively proven.