Dominant cone dystrophy

Figure 5. Cartoon of the human GC1 gene and GC1 disease mutations. In general, null mutations are associated with recessive LCA, whereas missense mutations in the dimerization domain are associated with dominant cone dystrophy...

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... 

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., Ohnishi, Y., and Miyake, Y. (2004b). Autosomal dominant cone-rod dystrophy with R838H and R838C mutations in the GUCY2D gene in Japanese patients. Jpn. J. Ophthalmol. 48 228-235. 

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. 

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). 

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. 

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...

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