Evidence of RPGRIP1 gene mutations associated with recessive cone-rod dystrophy

Open Access
Publisher Website
Google Scholar
Abstract
Cone-rod dystrophies (CRD) are forms of inherited retinal dystrophy which characteristically lead to early impairment of vision. An initial loss of colour vision (cone mediated functions) and of visual acuity, usually from the first or second decade of life, is followed by night blindness (largely rod mediated) and loss of peripheral visual fields.1 CRD patients suffer from severe photophobia and show reduced ERG responses. In later life, vision may be reduced to a bare perception of light. CRD is a milder condition compared to Leber congenital amaurosis (LCA) which is the most severe form of all the inherited retinal dystrophies and is diagnosed as bilateral congenital blindness, with a diminished or absent electroretinogram (ERG). Cone-rod dystrophy loci have been mapped to chromosomes 17q,2 19q,3 18q,4 17p13,5,6 6q,7 1q12,8 and 8p11.9 Mutations in the peripherin/RDS ,10 CRX ,11,12 and RetGC-I 13,14 genes have been shown to cause autosomal dominant CRD. Mutations in the ATP binding cassette transporter rim protein ( ABCR) gene have been shown to be associated with autosomal recessive CRD.15 Mutations in the CNGA3 gene encoding the α-subunit of the cone photoreceptor cGMP gated channel have also been reported to cause cone photoreceptor disorders.16 The RPGRIP1 protein (retinitis pigmentosa GTPase regulator interacting protein 1, MIM 605446) is encoded by the gene located on chromosome 14q11. It consists of 24 exons and the predicted size of its protein product is 1259 amino acids. It is expressed specifically in the rod and cone photoreceptors and is a structural component of the ciliary axoneme. One of its functions is to anchor the RPGR protein within the photoreceptor connecting cilium.17 Recently, in an in vivo investigation of RPGRIP1 function and its physical interaction, it has been shown that …