Cone-rod dystrophy (CORD) characteristically leads to early impairment of vision. An initial loss of color vision and of visual acuity is followed by nyctalopia (night blindness) and loss of peripheral visual fields. In extreme cases, these progressive symptoms ... Cone-rod dystrophy (CORD) characteristically leads to early impairment of vision. An initial loss of color vision and of visual acuity is followed by nyctalopia (night blindness) and loss of peripheral visual fields. In extreme cases, these progressive symptoms are accompanied by widespread, advancing retinal pigmentation and chorioretinal atrophy of the central and peripheral retina (Moore, 1992). In many families, perhaps a majority, atrophy of the central and peripheral chorioretinal atrophy is not found (Tzekov, 1998). - Genetic Heterogeneity of Autosomal Cone-Rod Dystrophy There are several other autosomal forms of CORD for which the molecular basis is known. CORD3 (604116) is caused by mutation in the ABCA4 gene (601691) on chromosome 1p21-p23. CORD5 (600977) is caused by mutation in the PITPNM3 gene (608921) on chromosome 17p13-p12. CORD6 (601777) is caused by mutation in the GUCY2D gene (600179) on chromosome 17p13.1. CORD7 (603649) is caused by mutation in the RIMS1 gene (606629) on chromosome 6q12-q13. CORD9 (612775) is caused by mutation in the ADAM9 gene (602713) on chromosome 8p11.23. CORD10 (610283) is caused by mutation in the SEMA4A gene (607292) on chromosome 1q22. CORD11 (610381) is caused by mutation in the RAXL1 gene (610362) on chromosome 19p13.3. CORD12 (612657) is caused by mutation in the PROM1 gene (604365) on chromosome 4p15. CORD13 (608194) is caused by mutation in the RPGRIP1 gene (605446) on chromosome 14q11. CORD14 (see 602093) is caused by mutation in the GUCA1A gene (600364) on chromosome 6p21.1. CORD15 (613660) is caused by mutation in the CDHR1 gene (609502) on chromosome 10q23.1. CORD16 (614500) is caused by mutation in the C8ORF37 gene (614477) on chromosome 8q22.1. CORD18 (615374) is caused by mutation in the RAB28 gene (612994) on chromosome 4p15. A diagnosis of CORD was made in an individual with a mutation in the AIPL1 gene (604392.0004) on chromosome 17p13.1, as well as in an individual with a mutation in the UNC119 gene (604011.0001) on chromosome 17q11.2. Other mapped loci for autosomal CORD include CORD1 (600624) on chromosome 18q21.1-q21.3; CORD8 (605549) on chromosome 1q12-q24; and CORD17 (615163) on chromosome 10q26. For a discussion of X-linked forms of cone-rod dystrophy, see CORDX1 (304020).
Hittner et al. (1975) described an extensively affected kindred with an autosomal dominant dystrophy of the retinal photoreceptors and pigment epithelium that is characterized by simultaneous abiotrophic degeneration of rods and cones. The onset of decreased central vision ... Hittner et al. (1975) described an extensively affected kindred with an autosomal dominant dystrophy of the retinal photoreceptors and pigment epithelium that is characterized by simultaneous abiotrophic degeneration of rods and cones. The onset of decreased central vision with concurrent progressive constriction of peripheral visual fields occurs prior to age 10. Unlike previously described cone dystrophies, there is an inexorable progression to no light perception. Ferrell et al. (1981) provided follow-up on the family reported by Hittner et al. (1975). In all, 25 affected persons had been identified. Evans et al. (1995) reported the clinical features of 34 affected members in 4 generations. Loss of visual acuity occurred in the first decade of life, onset of night blindness occurred after 20 years of age, and little visual function remained after the age of 50 years. Central and, later, peripheral retinal fundus changes were associated with central scotoma, pseudoaltitudinal field defects, and finally, global loss of function. Psychophysical and electrophysiologic testing before the age of 26 years showed more marked loss of cone than of rod function. Evans et al. (1995) found complete blindness (no light perception) in only 3 of the 34 patients studied, and these 3 were all over 65 years of age. Serious effects on visual acuity (light perception only) were present in 10 other patients; however, their mean age was 60.3 years. All other patients retained some visual acuity. Papaioannou et al. (1998) reported a 4-generation family of Greek origin with clinical features similar to those described in the British family by Evans et al. (1994). Itabashi et al. (2004) characterized the clinical features of a Japanese family with CORD. The ophthalmic findings included CORD with negative-type electroretinograms (ERGs) and a rapid progression after age 40 years. The authors concluded that genotype-phenotype correlation in the CRX gene in their patient and others reported in the literature suggested that the negative-type ERG might be indicative of a mutation in the CRX gene.
In affected members of 2 pedigrees with CORD2, Freund et al. (1997) identified a missense and a frameshift mutation in the CRX gene, an OTX-like homeobox gene. The authors showed that the missense mutation (602225.0001) was not a ... In affected members of 2 pedigrees with CORD2, Freund et al. (1997) identified a missense and a frameshift mutation in the CRX gene, an OTX-like homeobox gene. The authors showed that the missense mutation (602225.0001) was not a polymorphic variant and concluded that mutation in the CRX gene is responsible for the CORD2 phenotype. In a Japanese family with CORD, Itabashi et al. (2004) found a 1-bp deletion in exon 1 of the CRX gene (602225.0009).