A Frame hift mutation in a tiue-pecific alternatively pliced exon of collagen 2A1 in Wagner’ vitreoretinal degeneration

PURPOE: To decribe the genetic bai of an autoomal dominant vitreoretinopathy in a large French-Canadian kindred. METHOD: A clinical cohort tudy followed by laboratory-baed genetic and molecular analyi. Thirty-two affected and 22 unaffected member of the kindred were examined. Candidate gene/region for Wagner’ dieae and tickler yndrome were teted for genetic linkage. Mutation analyi wa carried out with direct PCR-baed equencing. REULT: Funducopic examination of 32 affected patient revealed optically clear vitreou, vitreou veil, and radial perivacular pigmentation. pondyloarthropathie or craniofacial abnormalitie were notably abent. There wa a 53% rate of retinal detachment that required urgical intervention. Genetic linkage wa obtained to COL2A1, the candidate gene for tickler’ type I. A frame hift mutation in exon 2, leading to early truncation of the protein (Cy57top), wa detected. CONCLUION: Wagner’ dieae in thi large kindred ha had devatating viual conequence. In affected individual, we found a novel COL2A1 frame hift mutation in exon 2. The mutation arie in an exon that i electively preent in vitreou collagen mRNA, but abent in cartilage mRNA through tiue-pecific alternative plicing. Tiue-pecific alternative plicing of COL2A1 mRNA thu provide an elegant biochemical mechanim for a clinical phenotype of Wagner’ dieae in thi kindred.