Retinal degeneration and Retinitis Pigmentosa

Retinal degenerations include the diagnosis of Retinitis Pigmentosa (RP), an inherited disorder that affects about 1 in 3000 newborns. RP constitutes a progressive retinal disease that features early-onset night blindness, concentric constriction of the visual field, midperipheral pigment deposits, and attenuation of retinal blood vessels. The disease causes visual impairment. RP often progresses towards blindness, although clinical variability is striking and may lead to different clinical presentations even among family members.
RP can be caused by mutations in more than 60 genes showing different inheritance patterns within family pedigrees (including autosomal recessive or autosomal dominant or X-chromosomal recessive traits).

Figure legend: Examples of retinal degenerations include macular degeneration, cone-rod degeneration, Leber´s congenital amaurosis or color vision defects. The pedigree and corresponding fundus/autofluoresence pictures are presented from a family in which macular degeneration shows phenotypic variability. We found a genotype-phenotype correlation indicating that genetic modifiers influence the expressivity of the phenotype. The mutation that co-segregates with the phenotype locates to the PRPH2 gene, whereas the severeness of the clinical presentation seems to be modified by a sequence variant in the ABCA4 gene.

X-Chromosomal retinal degeneration

Only two X-chromosomal genes are known to cause Retinitis pigmentosa: RP2 and RPGR (Retinitis Pigmentosa GTPase regulator). We and others have shown that mutations in the RP2 and RPGR genes lead to Retinitis pigmentosa. RPGR may even cause different forms of retinal degenerations (Retinitis Pigmentosa, Cone Dystrophy, and Macular Degeneration) and the clinical presentation due to RPGR mutations can show substantial variability of symptoms.
RP2 and RPGR are located on the X-chromosome and frequently affect male patients. Nevertheless, in some families segregating RPGR mutations, both males and female carriers are affected.
In collaboration with clinicians, we offer the research-based analysis of family pedigrees and genetic testing of affected patients and families. A detailed characterization of the pathogenic processes in cell culture assays can also be offered. The results of these analyses are the basis to develop therapeutic approaches.