Hereditary vascular retinopathy, cerebroretinal vasculopathy, and hereditary endotheliopathy with retinopathy, nephropathy, and stroke map to a single locus on chromosome 3p21.1-p21.3

We performed a genomewide search for linkage in an extended Dutch family wi th hereditary vascular retinopathy associated with migraine and Raynaud phe nomenon. Patients with vascular retinopathy are characterized by microangio pathy of the retina, accompanied by microaneurysms and telangiectatic capil laries. The genome search, using a high throughput capillary sequencer, rev ealed significant evidence of linkage to chromosome 3p21.1-p21.3 (maximum p airwise LOD score 5.25, with D3S1578). Testing of two additional families t hat had a similar phenotype, cerebroretinal vasculopathy, and hereditary en dotheliopathy with retinopathy, nephropathy, and stroke, revealed linkage t o the same chromosomal region (combined maximum LOD score 6.30, with D3S158 8). Haplotype analysis of all three families defined a 3-cM candidate regio n between D3S1578 and D3S3564. Our study shows that three autosomal dominan t vasculopathy syndromes with prominent cerebroretinal manifestations map t o the same 3-cM interval on 3p21, suggesting a common locus.