The crd2 gene encodes a protein that is part of the tumor necrosis factor (TNF) superfamily and contains cysteine rich domains which are essential for binding to the ligands APRIL and BAFF. It is known that TACI binds these ligands with high affinity by forming homo- or heterodimers with its partner proteins TRAIL and TRAF2 and the complexes are rapidly degraded by proteases. The gene for TACI also encodes the cysteine-rich domain 2 of the receptor, a component that mediates the interaction between TNFR and the ligands.

Most CRDs result from mutations in the CRX gene that codes for the homeobox protein CRX, which is required for both rod and cone photoreceptor cell differentiation and survival. Mutations in CRX cause autosomal dominant CRD and may also lead to Leber congenital amaurosis (LCA), a more severe form of the disease. Mutations in two other genes, RIM1 and HRG4, have also been found in cases of autosomal dominant CRD. These mutations cause LCA and may also lead to recessive RP.

Another category of CRDs is caused by mutations in the genes encoding the proteins involved in the outer segment of the retina. Most of these are inherited in an autosomal dominant manner and are usually associated with a moderate type of RP. Mutations in the gene for the outer segment protein peripherin/RDS (which is involved in the trafficking of opsins) have been associated with autosomal dominant CRD. Mutations in the gene for the other protein involved in the outer segment, RPGR (which is necessary for photoreceptor synaptic transmission), have been associated with recessive RP.

Other conditions with CRDs include spinocerebellar ataxia, amelogenesis imperfecta and cleft lip and palate. The phenotypes of these are different from the typical RP but the retinal degeneration is similar.More Details Crd2

In the most common type of CRD, RP1, the first symptom is typically night blindness that gradually worsens over several years. Affected individuals may notice a dark spot in the center of their field of vision (the fovea centralis) or a change in the brightness of light or color that occurs when looking directly at it (color blindness). The progression is slow, and macular involvement typically does not occur until late in the disease.

Molecular testing is available to confirm the diagnosis of CRD. In CRDs due to the stargardt gene, ABCA4, a disease history characterized by progressive loss of visual acuity in low lighting and the finding of yellow flecks in the fundus on fluorescein angiography confirm the diagnosis. Similarly, molecular testing is often performed for the other genes involved in autosomal dominant CRDs: CRX, ABCA4, GUC1A and GUCY2D. The results of this testing can be used to confirm the diagnosis and help in selecting appropriate therapies.