ORPHA: 1872; DO: 0111012;
Cytogenetic location: 6q14 Genomic coordinates (GRCh38) : 6:75,200,001-87,300,000
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 6q14 | Cone-rod dystrophy 7 | 603649 | Autosomal dominant | 2 |
For a general phenotypic description and a discussion of genetic heterogeneity of cone-rod dystrophy, see 120970.
Kniazeva et al. (1999) examined 10 members of a 4-generation family segregating an autosomal dominant form of macular dystrophy and identified 5 individuals with characteristic features of cone-rod dystrophy and Stargardt disease; a sixth family member (deceased) was classified as affected by history. Most affected individuals had gradual onset of decreased visual acuity during the fourth decade, bilateral macular atrophy, diffusely abnormal ERG responses, and markedly reduced color vision. In addition, several affected individuals demonstrated features highly suggestive of Stargardt-like disease (see 600110), such as yellow 'flavimaculatus flecks' in the retinal pigment epithelium and a 'dark choroid' pattern on fluorescein angiography.
In a 4-generation family segregating autosomal dominant cone-rod dystrophy with features of Stargardt disease, Kniazeva et al. (1999) performed linkage analysis using DNA markers linked to known loci for cone-rod dystrophy and dominant Stargardt disease and obtained a maximum lod score of 3.3 (theta = 0.010) at marker D6S280 on chromosome 6q14. A recombination event in the family defined marker D6S284 as the telomeric marker for the genetic interval.
Reclassified Variants
The R820H mutation in the RIMS1 gene (606629.0001) was reclassified as a variant of unknown significance. In 6 affected members of a 4-generation British family described by Kelsell et al. (1998) as having CORD7 on chromosome 6, Johnson et al. (2003) identified heterozygosity for a missense mutation in the RIMS1 gene (R820H; 606629.0001). The mutation was not found in 3 unaffected members of the family or in 115 ethnically matched controls. In a restudy of this family, a mutation in the PROM1 gene (604365.0003) on chromosome 4 was identified.
Kelsell et al. (1998) mapped a form of autosomal dominant cone-rod dystrophy to chromosome 6q in a 4-generation British family. Two-point linkage data for the family excluded the 6p12 region occupied by the gene encoding peripherin/RDS (PRPH2; 179605) and the 6q14-q16.2 region occupied by the genes for North Carolina macular dystrophy (MCDR1; 136550) and progressive bifocal chorioretinal atrophy (PBCRA; 600790). Haplotype analysis localized the disease-causing locus, designated CORD7, between D6S430 and D6S1625, a region estimated to be 7 cM.
Johnson, S., Halford, S., Morris, A. G., Patel, R. J., Wilkie, S. E., Hardcastle, A. J., Moore, A. T., Zhang, K., Hunt, D. M. Genomic organisation and alternative splicing of human RIM1, a gene implicated in autosomal dominant cone-rod dystrophy (CORD7). Genomics 81: 304-314, 2003. [PubMed: 12659814] [Full Text: https://doi.org/10.1016/s0888-7543(03)00010-7]
Kelsell, R. E., Gregory-Evans, K., Gregory-Evans, C. Y., Holder, G. E., Jay, M. R., Weber, B. H. F., Moore, A. T., Bird, A. C., Hunt, D. M. Localization of a gene (CORD7) for a dominant cone-rod dystrophy to chromosome 6q. (Letter) Am. J. Hum. Genet. 63: 274-279, 1998. [PubMed: 9634506] [Full Text: https://doi.org/10.1086/301905]
Kniazeva, M., Chiang, M. F., Cutting, G. R., Zack, D. J., Han, M., Zhang, K. Clinical and genetic studies of an autosomal dominant cone-rod dystrophy with features of Stargardt disease. Ophthal. Genet. 20: 71-81, 1999. [PubMed: 10420191] [Full Text: https://doi.org/10.1076/opge.20.2.71.2287]