Background: Wagner disease and erosive vitreoretinopathy are potentially blinding autosomal dominant diseases that share some similarities with 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 families with COL2A1-associated Stickler syndrome. In addition, rhegmatogenous 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 of the genes involved in Wagner disease and erosive vitreoretinopathy and to distinguish these conditions genetically from Stickler syndrome.
Methods: Fifteen affected members of a family affected with erosive vitreoretinopathy and 24 affected descendants of the pedigree described by Wagner were genotyped with a set of short tandem repeat polymorphisms distributed across the genome.
Results: Significant linkage was observed in each family between the disease phenotype and markers that map to chromosome 5q13-14. The highest lod score for the family affected 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 the linked interval was screened for mutations, but none was found in either family.
Conclusions: These data suggest that erosive vitreoretinopathy and Wagner disease are allelic disorders and demonstrate that they are genetically distinct from COL2A1-associated Stickler syndrome.