Retinitis Pigmentosa 41
A number sign (#) is used with this entry because of evidence that autosomal recessive retinitis pigmentosa-41 (RP41) is caused by homozygous mutation in the PROM1 gene (604365) on chromosome 4p15.
For a phenotypic description and a discussion of genetic heterogeneity of retinitis pigmentosa, see 268000.
Clinical FeaturesMaw et al. (2000) reported a consanguineous Indian family in which 4 of 8 sibs had night blindness and loss of peripheral vision from childhood with progression to profound visual impairment and extinguished electroretinograms (ERG) by their third decade. Fundus examination revealed narrowed arteries, optic disc pallor, pigment deposits, and macular degeneration. One sister also had polydactyly on one foot. Polydactyly and retinal degeneration are manifestations of Bardet-Biedl syndrome (see 209900); however, the authors stated that none of the other manifestations of that disorder were present in this family.
Zhang et al. (2007) described a consanguineous Pakistani family with a severe form of retinitis pigmentosa accompanied by macular degeneration. Rod and cone responses on ERG were extinguished in the second decade. Fundus examination revealed waxy-pale discs, obvious attenuation of the retinal arteries, macular degeneration, and typical bone-spicule pigmentation in the midperipheral retina in all 6 affected individuals. Atrophy of the choriocapillaris and posterior retinal pigment epithelium allowed visualization of the large choroidal vessels in patients over age 40 years. None of the affected individuals had polydactyly or other systemic abnormalities.
MappingMaw et al. (2000) performed linkage analysis in the consanguineous Indian family with retinal degeneration and narrowed the locus to chromosome 4p. Markers distal to D4S1602 formed a haplotype that cosegregated with the disorder. Crossovers indicated that the critical region was proximal to D4S2960 and distal to D4S1567. This region was found to be distinct from the distal PDEB (180072) region at 4p16.3 and the proximal CNGA1 (123825) region at 4p12-cen; both of these genes had previously been implicated in autosomal recessive retinal degeneration. A 2-point maximum lod score of 3.17 at theta = 0.00 was obtained for markers within the PROM1 gene.
Zhang et al. (2007) performed a genomewide scan in the consanguineous Pakistani family with severe retinitis pigmentosa and mapped the disease to a 34.7-cM region of chromosome 4p16-p14 between D4S1599 and D4S405 (maximum lod score of 3.96 at theta = 0 with D4S403 and D4S391).
Molecular GeneticsIn affected members of a consanguineous Indian family with retinal degeneration, Maw et al. (2000) identified homozygosity for a 1-bp deletion in the PROM1 gene (604365.0001), predicted to cause truncation of the protein. The mutation was not found in 97 Indian controls.
In all 6 affected members of a consanguineous Pakistani family with severe retinitis pigmentosa, Zhang et al. (2007) identified homozygosity for a nonsense mutation in the PROM1 gene (604365.0002). Five of 6 unaffected family members were heterozygous for the mutation, which was not found in 192 ethnically matched unrelated controls from the same region.