Clinical and genetic studies of an autosomal dominant cone-rod dystrophy with features of Stargardt disease.

Kniazeva MF, Chiang MF, Cutting GR, Zack DJ, Han M, Zhang K.


Department of Molecular, Cellular and Developmental Biology, Howard Hughes Medical Institute, University of Colorado, Boulder, USA.

Ophthalmic Genet. 1999 Jun;20(2):69-70 


                              Cone-rod dystrophy (CORD) and Stargardt disease (STGD) are two hereditary retinal dystrophies with similarities to age-related macular
                              degeneration. Cone-rod dystrophies are a group of degenerative disorders resulting in decreased visual acuity and color vision, attenuated
                              electroretinographic (ERG) responses, and atrophic macular lesions. Autosomal dominant, autosomal recessive, and X-linked forms of cone-rod
                              dystrophy have been reported. Stargardt disease is characterized by reduced visual acuity, atrophic macular changes, prominent 'flavimaculatus
                              flecks' in the pigment epithelium of the posterior retina, and a virtually pathognomic 'dark choroid' pattern on fluorescein angiography. Stargardt
                              disease is classically inherited as an autosomal recessive trait, although numerous families have been described in which features of Stargardt
                              disease are transmitted in an autosomal dominant manner. We have identified a new kindred with autosomal dominant cone-rod dystrophy with
                              features of Stargardt-like disease. Detailed clinical evaluation, genotype analysis, and linkage analysis were performed. Fluorescein angiography
                              revealed a 'dark choroid' pattern in three affected subjects. Electroretinography disclosed markedly reduced scotopic and photopic responses in
                              three affected individuals. Genetic analysis revealed linkage to known loci for cone-rod dystrophy (CORD7) and Stargardt-like disease
                              (STGD3) on chromosome 6q14. A peak lod score of 3.3 was obtained with the marker D6S280 at straight theta =0.010. A physical map was
                              constructed by screening a YAC library with short tandem repeat markers in the region. Screening of a candidate gene, the rho1 subunit of the
                              GABA receptor, failed to reveal any mutations.