GENETIC-LINKAGE OF WAGNER DISEASE AND EROSIVE VITREORETINOPATHY TO CHROMOSOME 5Q13-14

Background: Wagner disease and erosive vitreoretinopathy are potential ly blinding autosomal dominant diseases that share some similarities w ith Stickler syndrome. However, both disorders have associated retinal pigment epithelial changes, poor night vision, visual field defects, and abnormal electroretinographic findings, which are not found in fam ilies with COL2A1-associated Stickler syndrome. In addition, rhegmatog enous retinal detachments are uncommon in Wagner disease but occur in approximately 50% of patients with either Stickler syndrome or erosive vitreoretinopathy. Objectives: To identify the chromosomal location o f the genes involved in Wagner disease and erosive vitreoretinopathy a nd to distinguish these conditions genetically from Stickler syndrome. Methods: Fifteen affected members of a family affected with erosive v itreoretinopathy and 24 affected descendants of the pedigree described by Wagner were genotyped with a set of short tandem repeat polymorphi sms distributed across the genome. Results: Significant linkage was ob served in each family between the disease phenotype and markers that m ap to chromosome 5q13-14. The highest lod score for the family affecte d with erosive vitreoretinopathy was 4.2 and was obtained with marker GATA3H06 (theta=0). The highest lod score for the family affected with Wagner disease was 5.8 and was obtained with marker D5S815 (theta=0). A candidate gene (cartilage link protein) that is known to lie near t he linked interval was screened for mutations, but none was found in e ither family. Conclusions: These data suggest that erosive vitreoretin opathy and Wagner disease are allelic disorders and demonstrate that t hey are genetically distinct from COL2A1-associated Stickler syndrome.