Rod-cone dystrophy

Calbindin D-28K is an example of a calcium-binding protein of the EF hand family that is not enriched through its calcium-dependent binding to phenyl-Sepharose. Instead, it can be readily purified by binding to DEAE-Sepharose in low calcium and eluted by increased calcium (Figure 2, lane h). Our studies demonstrate that calbindin D-28K is expressed in peripheral and perifoveal cone cells of the human retina but not in parafoveal or foveal cones, and this pattern of expression parallels the degeneration of photoreceptor cells seen in some humans with rod-cone dystrophies. 

The ribbon is composed mainly of the structural protein, Ribeye, but also includes a kinesin motor protein, KIF3A, and Rab3-interacting protein, RIM. Ribbons are attached to the synaptic active zone by bassoon, and its structural relative, piccolo. Although the ribbon appears to anchor a readily releasable pool of vesicles, molecular motors do not appear to be involved in vesicle movements near the active zone. RDVt protein mutations have been implicated in an autosomal dominant rod-cone dystrophy (Johnson et al., 2003). 

GCAP1(L151F) mutations affecting the EF4-hand motif linked to dominant cone dystrophy and cone-rod dystrophy were identified in two unrelated families. In one family (Sokal et al., 2004), affected family members experienced dyschro-matopsia, hemeralopia, and reduced visual acuity by the second to third decade... 

In vitro experiments showed that GCAP1 effectively stimulates mostly GC1, whereas GCAP2 and GCAP3 stimulate both GC1 and GC2 (Haeseleer et al., 1999) (Figure 4). A mutation associated with a cone-rod dystrophy in the... 

Table 1. Selected pathogenic mutations in GC1 (Additional mutations can be found in (Hanein et al., 2004)). LCA1, Leber congenital amaurosis type 1 ar, autosomal recessive ad, autosomal dominant RP, retinitis pigmentosa CORD, cone-rod dystrophy IRP, juvenile isolated RP fs, frameshift mis, missense splice, splice site mutation non, nonsense mutation...

Downes, S.M., Holder, G.E., Fitzke, F.W., Payne, A.M., Warren, M.J., Bhattacharya, S.S., and Bird, A.C. (2001a). Autosomal dominant cone and cone-rod dystrophy with mutations in the guanylate cyclase activator 1A gene-encoding guanylate cyclase activating protein-1. Arch. Ophthalmol. 119 96-105. 

Ito, S., Nakamura, M., Nuno, Y., Ohnishi, Y., Nishida, T., and Miyake, Y. (2004a). Novel complex GUCY2D mutation in Japanese family with cone-rod dystrophy. Invest Ophthalmol. Vis. Sci 45 1480-1485. 

Michaelides, M., Wilkie, S.E., Jenkins, S., Holder, G.E., Hunt, D.M., Moore, A.T., and Webster, A.R. (2005). Mutation in the gene GUCA1A, encoding guanylate cyclase-activating protein 1, causes cone, cone-rod, and macular dystrophy. Ophthalmology 112 1442-1447. 

Sokal, I., Dupps, W.J., Andorf, J.A., Schrum, K.M., Melendez, K.A., Roychowdhury, N., Yang, L., Filipek, S., Palczewski, K., Stone, E.M., and Baehr, W. (2004). A Novel GCAP1 Missense Mutation (L151F) in a Large Family with Autosomal Dominant Cone-Rod Dystrophy. Invest Ophthalmol. Vis. Sci submitted. 

Tucker, C.L., Woodcock, S.C., Kelsell, R.E., Ramamurthy, V., Hunt, D.M., and Hurley, J.B. (1999). Biochemical analysis of a dimerization domain mutation in RetGC-1 associated with dominant cone-rod dystrophy. Proc. Natl. Acad. Sci. U. S. A 96 9039-9044. 

Brown J, Jr., Kimura AE, Gorin MB (2000) Clinical and electroretinographic findings of female carriers and affected males in a progressive X-linked cone-rod dystrophy (COD-1) pedigree. Ophthalmology 107 1104-1110. 

Jalkanen R, Mantyjarvi M, Tobias R, Isosomppi J, Sankila EM, Alitalo T, Bech-Hansen NT (2006) X-linked cone-rod dystrophy, CORDX3, is caused by a mutation in the CACNA1F gene. J Med Genet. 

Johnson S, Halford S, Morris AG, Patel RJ, Wilkie SE, Hardcastle AJ, Moore AT, Zhang K, Hunt DM (2003) Genomic organisation and alternative splicing of human RIMl, a gene implicated in autosomal dominant cone-rod dystrophy (CORD7). Genomics 81 304-314. 

Functional characterization of missense mutations at codon 838 in retinal guanylate cyclase correlates with disease severity in patients with autosomal dominant cone-rod dystrophy. Hum Mol Genet 9 3065-3073. 

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