Small and Gehrs (1996) studied a family from eastern Tennessee in which 34 members in multiple generations had what the authors called 'autosomal dominant progressive cone degeneration.' Symptoms generally began in the first decade of life and slowly ... Small and Gehrs (1996) studied a family from eastern Tennessee in which 34 members in multiple generations had what the authors called 'autosomal dominant progressive cone degeneration.' Symptoms generally began in the first decade of life and slowly progressed into midlife. Ophthalmoscopic findings consisted primarily of macular granularity or central macular atrophy. The photopic full-field electroretinogram (ERG) was important in establishing the diagnosis, although the results of the ERG measurements varied among individuals. Either the foveal ERG amplitudes were abnormally low or the foveal/parafoveal ratio was abnormal in all affected individuals. The authors commented that no single test or finding was completely sensitive or specific for accurate diagnosis of the condition. Especially in the more mildly affected subjects, a constellation of symptoms, findings, and test results were used to diagnose autosomal dominant cone degeneration. Gregory-Evans et al. (2000) described the clinical features of the family originally linked to CORD6 by Kelsell et al. (1997). In addition to childhood-onset clinical and electroretinographic features of CORD, moderate myopia and pendular nystagmus were seen in affected individuals. Of the 10 affected family members studied, an electroretinogram (ERG) was recordable in the 4 youngest (ages 14 to 47 years). In all 4 individuals, the cone ERG was more severely affected than the rod ERG. Color vision testing was possible in the youngest affected family member (age 14); it revealed no blue discrimination but retention of significant red-green discrimination. The authors concluded that the CRD phenotype associated with GUCY2D is clinically distinct from that associated with other dominant CRD loci. They postulated that the unusual electroretinographic responses may indicate that this mutation of GUCY2D is associated with early defects in photoreceptor synaptic transmission to second-order neurons. Ugur Iseri et al. (2010) reported a consanguineous Turkish family segregating autosomal recessive CORD, with 6 affected members over 2 generations. All affected individuals had dramatically reduced visual acuity, dyschromatopsia, and nyctalopia, together with variable presentation of photophobia, bone spicule formation, retinal vessel attenuation, retinal degeneration, and macular and chorioretinal atrophy with decreased cone and rod responses on ERGs. None of the patients was blind at birth, rather having reduced but stable vision loss according to family history.
Downes et al. (2001) described the phenotype and electrophysiologic responses in 4 British families, 3 with an R838C mutation (600179.0006) and 1 with an R838H mutation (600179.0008) in the GUCY2D gene. Although subjects had lifelong poor vision in ... Downes et al. (2001) described the phenotype and electrophysiologic responses in 4 British families, 3 with an R838C mutation (600179.0006) and 1 with an R838H mutation (600179.0008) in the GUCY2D gene. Although subjects had lifelong poor vision in bright light, a major reduction in visual acuity did not occur in most of them until after their late teens. Fundus abnormalities were confined to the central macula, and increasing central atrophy was noted with age. Electrophysiologic testing revealed a marked loss of cone function with only minimal rod involvement, even in older subjects. The authors concluded that the phenotype associated with autosomal dominant cone-rod dystrophy with either an R838C or R838H mutation in GUCY2D was distinctive, with predominantly cone system involvement. There was some variation in severity within the 3 families with the R838C mutation. Families with the R838C or R838H mutations had a much milder phenotype than the families previously described with the E837D/R838S mutation (600179.0005) in GUCY2D.
In the British family originally reported by Kelsell et al. (1997) and in 3 unrelated families with cone-rod dystrophy, Kelsell et al. (1998) identified 2 different heterozygous mutations in the GUCY2D gene (600179.0005 and 600179.0006, respectively).
... In the British family originally reported by Kelsell et al. (1997) and in 3 unrelated families with cone-rod dystrophy, Kelsell et al. (1998) identified 2 different heterozygous mutations in the GUCY2D gene (600179.0005 and 600179.0006, respectively). Udar et al. (2003) sequenced the entire GUCY2D gene in an affected individual from each of 2 families with cone dystrophy, 1 of which was the eastern Tennessee family originally reported by Small and Gehrs (1996), and identified a heterozygous mutation in each (600179.0006 and 600179.0008, respectively). In affected members of a consanguineous Turkish family segregating autosomal recessive CORD mapping to chromosome 17p13.3-p11.2, Ugur Iseri et al. (2010) identified homozygosity for a missense mutation (600179.0010) in the GUCY2D gene.