Progressive cone dystrophy usually presents in childhood or early adult life, with many patients developing rod photoreceptor involvement in later life, thereby leading to considerable overlap between progressive cone dystrophy and cone-rod dystrophy. Both progressive cone dystrophy and ... Progressive cone dystrophy usually presents in childhood or early adult life, with many patients developing rod photoreceptor involvement in later life, thereby leading to considerable overlap between progressive cone dystrophy and cone-rod dystrophy. Both progressive cone dystrophy and cone-rod dystrophy have been associated with mutation in the GUCA1A gene (Michaelides et al., 2006).
Payne et al. (1997) described a 4-generation British family with typical clinical features of autosomal dominant cone dystrophy with photophobia, loss of color and central vision, and distinctive electrophysiologic findings.
Payne et al. (1998) further studied ... Payne et al. (1997) described a 4-generation British family with typical clinical features of autosomal dominant cone dystrophy with photophobia, loss of color and central vision, and distinctive electrophysiologic findings. Payne et al. (1998) further studied the family described by Payne et al. (1997). Twenty-seven members were shown to be affected by clinical examination. There was some variability of expression. The initial symptom of reduced visual acuity associated with loss of color vision became apparent between the ages of 20 and 40 years. Changes at the level of the retinal pigment epithelium at the macula were identified before visual loss. Central atrophy developed with time. Visual field testing showed central loss with preservation of peripheral visual fields, even in late disease. Electrophysiologic testing revealed significant generalized loss of cone function as shown by reduction in photopic electroretinograms (ERG), and central retinal involvement as shown by reduction in pattern ERGs. Holopigian et al. (2002) compared the patterns of local cone and rod system impairment in patients with progressive cone dystrophy using psychophysical and electrophysiologic techniques. The authors found poor correspondence among local measures of cone and rod system losses in their patients with progressive cone dystrophy. The results suggested that the spatial pattern of cone system losses in progressive cone dystrophy differed from the spatial pattern of rod system losses.
In the same 4-generation British family, Payne et al. (1998) screened the GUCA1A gene, which encodes a calcium-binding protein that is highly expressed in photoreceptor outer segments, and identified a tyr99-to-cys mutation (Y99C; 600364.0001).
Michaelides et ... In the same 4-generation British family, Payne et al. (1998) screened the GUCA1A gene, which encodes a calcium-binding protein that is highly expressed in photoreceptor outer segments, and identified a tyr99-to-cys mutation (Y99C; 600364.0001). Michaelides et al. (2005) reported a 4-generation British family in which affected individuals presented with cone dystrophy, cone-rod dystrophy (CORD14), or isolated macular dysfunction. The Y99C mutation was found in all affected individuals. In a family with autosomal dominant cone-rod dystrophy (CORD14), Sokal et al. (2005) identified an L151F mutation (600364.0003) in the GUCA1A gene. Affected family members experienced dyschromatopsia, hemeralopia, and reduced visual acuity by the second to third decade of life. The clinical phenotype was characterized by early cone dysfunction and a progressive loss of rod function as shown by electrophysiology, which revealed a nonrecordable photopic response with later attenuation of the scotopic response. The biochemical phenotype was best described as persistent stimulation of photoreceptor guanylate cyclase, representing a gain of function of mutant GUCA1A. In a 5-generation family with autosomal dominant cone dystrophy, Jiang et al. (2005) identified the L151F mutation. Sokal et al. (2005) commented that the reason for the discrepancy in phenotype was unclear.