Total colorblindness, also referred to as rod monochromacy or complete achromatopsia, is a rare congenital autosomal recessive disorder characterized by photophobia, reduced visual acuity, nystagmus, and the complete inability to discriminate between colors. Electroretinographic recordings show that in ... Total colorblindness, also referred to as rod monochromacy or complete achromatopsia, is a rare congenital autosomal recessive disorder characterized by photophobia, reduced visual acuity, nystagmus, and the complete inability to discriminate between colors. Electroretinographic recordings show that in achromatopsia the rod photoreceptor function is normal, whereas cone photoreceptor responses are absent (summary by Kohl et al., 1998). - Genetic Heterogeneity of Total Achromatopsia A form of achromatopsia previously designated achromatopsia-1 (ACHM1) was later found to the same as achromatopsia-3 (ACHM3; 262300), caused by mutation in the CNGB3 gene (605080); ACHM4 (613856) is caused by mutation in the GNAT2 gene (139340); and ACHM5 (613093) is caused by mutation in the PDE6C gene (600827).
Patients with achromatopsia have poor visual acuity, photophobia, congenital nystagmus, and colorblindness. Photophobia is striking, even in light of ordinary intensity. Vision in ordinary light is severely restricted, and relatively better in dim light. The fundus appears normal ... Patients with achromatopsia have poor visual acuity, photophobia, congenital nystagmus, and colorblindness. Photophobia is striking, even in light of ordinary intensity. Vision in ordinary light is severely restricted, and relatively better in dim light. The fundus appears normal (summary by Zlotogora, 1995). The largest pedigree reported with achromatopsia is that of a family residing on the Island of Fuur in the Limfjord in the north of Denmark (Holm and Lodberg, 1940; Franceschetti et al., 1963). Mantyjarvi (1978) described affected brothers and a sister with first-cousin parents. Sloan (1954) observed second-cousin parents in 2 instances. Voke-Fletcher (1978) described affected brother and sister with first-cousin parents. Both sibs had marked lateral nystagmus and photophobia. Typical rod monochromats have normal levels of rhodopsin and normal rod function but lack all sensitivity mediated by cone pigments. Some atypical rod monochromats behave as if they have only rod vision; however, reflection densitometry shows that their retinas contain normal quantities of cone pigments (Alpern, 1974), suggesting that the defect is located distal to the point of light absorption. Presumably the site of the mutation in this disorder is different from that in total colorblindness. Simunovic et al. (2001) examined red-green color-deficient subjects, a small sample of monochromats, and age-matched color-normal control subjects to determine whether color vision deficiency confers a selective advantage under scotopic conditions. They found no evidence that red-green color deficiency or monochromatism confers a selective advantage under scotopic conditions, including dark adaptation, scotopic visual field sensitivity, or performance on a scotopic perceptual task. Using optical coherence tomography, Varsanyi et al. (2007) examined in vivo the anatomic structure of the retina in patients with achromatopsia and controls. In patients with achromatopsia, statistically significant reductions were found in total macular volume and in the thickness of the central retina compared with controls. Varsanyi et al. (2007) stated that a possible reason for the structural alteration is the qualitative and/or quantitative disorder of the cone photoreceptors, as the morphologic change is most expressed in the foveola.
Kohl et al. (1998) identified missense mutations (600053.0001-600053.0005) in CNGA3 in 5 families with rod monochromacy. In 2 families the mutations were homozygous, whereas the remaining families showed compound heterozygous mutations. In all cases, the segregation pattern was ... Kohl et al. (1998) identified missense mutations (600053.0001-600053.0005) in CNGA3 in 5 families with rod monochromacy. In 2 families the mutations were homozygous, whereas the remaining families showed compound heterozygous mutations. In all cases, the segregation pattern was consistent with autosomal recessive inheritance of the disease. This was the first report of a color vision disorder caused by defects other than mutations in the cone pigment genes, and implied, at least in this instance, a common genetic basis for phototransduction in the 3 different cone photoreceptors of the human retina. Wissinger et al. (2001) screened for CNGA3 mutations in 258 independent families with hereditary cone photoreceptor disorders and found CNGA3 mutations not only in patients with the complete form of achromatopsia, but also in patients with incomplete achromatopsia and even in a few patients diagnosed with severe progressive cone dystrophy. Mutations were identified in 53 families and included 8 previously described mutations and 38 novel mutations. These mutations comprised 39 amino acid substitutions, 4 stop-codon mutations, two 1-bp insertions, and one 3-bp in-frame deletion. Most of the amino acid substitutions affected residues conserved in the CNG channel family and were clustered at the cytoplasmic face of transmembrane domains (TM) S1 and S2, in TM S4, and in the cGMP-binding domain. Four mutations, arg277 to cys (R277C; 600053.0009), arg283 to trp (R283W; 600053.0002), arg436 to trp (R435W; 600053.0010), and phe547 to leu (F547L; 600053.0006), accounted for 41.8% of all the detected mutations. Wiszniewski et al. (2007) analyzed the CNGA3, CNGB3, and GNAT2 (139340) genes in 16 unrelated patients with autosomal recessive ACHM: 10 patients had mutations in CNGB3, 3 had mutations in CNGA3, and no coding region mutations were found in 3 patients. The authors concluded that CNGA3 and CNGB3 mutations are responsible for the substantial majority of achromatopsia. Zelinger et al. (2010) identified a mutation in the CNGA3 gene (V529M; 600053.0008) in Arab Muslim and Oriental Jewish families with achromatopsia; the mutation was also identified in 3 previously unreported Christian European families. The European patients were all compound heterozygous for V529M and another CNGA3 mutation, whereas most of the Arab Muslim and Jewish patients were homozygous for V529M. Haplotype analysis revealed a shared Muslim-Jewish haplotype, which was different from the haplotypes detected in European patients; microsatellite analysis of the surrounding 21.5-cM interval on chromosome 2 revealed a unique and extremely rare haplotype associated with the V529M mutation. The shared mutation was calculated to have arisen about 200 generations earlier, in an ancient common ancestor who lived approximately 5,000 years ago.