Non-syndromic cone-rod dystrophies can be either autosomal dominant, autosomal recessive or X-linked and are caused by defects in at least 17 different genes. This database entry discusses only the autosomal disorders. See X-linked cone-rod dystrophies in a separate entry.
Cone-rod dystrophies inherited in an autosomal dominant pattern include:
CORD2 (120970) is caused by mutations in CRX at 19q13.3, a homeobox gene responsible for the development of photoreceptor cells. These are responsible for 5-10% of autosomal dominant cone-rod dystrophy cases (602225) and can also cause one type (LCA7) of Leber congenital amaurosis (602225) and a late-onset retinitis pigmentosa phenotype.
CORD5 (600977) is caused by mutations in the PITPNM3 gene at 17p13.1.
CORD6 (601777) is caused by a mutation in GUCY2D in a similar location on chromosome 17.
CORD7 (603649) is caused by mutations in RIMS1 at 6q12-q13.
Mutations in AIPL1 (604392), located in the same region, usually causes a form of Leber congenital amaurosis (LCA4) as well as retinitis pigmentosa (604393) but has also been reported in a cone-rod pigmentary retinopathy.
CORD11 (610381) is caused by mutations in RAXL1 (19p13.3).
CORD12 (612657) results from mutations in the PROM1 gene (4p15.3).
Mutations in the gene GUCA1A on chromosome 6p21.1 causes CORD14 (602093).
An as yet unclassified autosomal dominant type of cone-rod dystrophy has recently been localized to 10q26.
Cone-rod dystrophies inherited in an autosomal recessive pattern include:
Mutations in ABCA4 at 1p21-p13 is responsible for 30-60% of cases of autosomal recessive CRD (CORD3; 604116) . ABCA4 is also known to cause autosomal recessive Stargardt disease.
CORD8 (605549) has been found in a single consanguineous family and the mutation localized to 1q12-q24.
ADAM9 (602713) at 8p11 and 8p11.23 contains mutations that have been shown to cause autosomal recessive CORD9 in several consanguineous families.
Mutations in RPGRIP1 (14q11) are responsible for CORD13 (608194).
The CDHR1 gene (10q23.1) contains mutations that cause CORD15 (613660).
Other autosomal CRD disorders are CORD1 (600624) described in a single individual and possibly those due to mutations in HRG4 at 17q11.2 (604011).
Syndromal cone-rod dystrophies:
Cone-rod dystrophy may also be associated with other syndromes, such as Bardet-Biedl syndrome (209900), or spinocerebellar ataxia Type 7 (164500), autosomal recessive amelogenesis imperfecta with cone-rod dystrophy or Jalili syndrome (217080), neurofibromatosis type I (162200), and hypotrichosis with juvenile macular dystrophy and alopecia (601553). Metabolic disorders associated with cone-rod dystrophy include Refsum disease with phytanic acid abnormality (266500) and Alport syndrome (301050).
Cone-Rod Dystrophy 19 (615860) has been associated with male infertility as the result of mutations in TTLL5 affecting both photoreceptors and sperm.