Identification of a top codon mutation in exon 2 of the collagen 2A1 gene in a large tickler yndrome family

PURPOE: To decribe the clinical feature and identify the mutation reponible for an autoomal dominant vitreoretinal degeneration occurring in a previouly unreported large family. DEIGN: Cohort tudy. METHOD: Family member were evaluated clinically over a 30-year period. Genealogical invetigation, genetic linkage to known vitreoretinal degeneration, and mutation creening of the COL2A1 gene were performed. REULT: We identified a ingle large family (2,384 total family member) with vitreoretinal degeneration panning 12 generation. We reviewed the clinical record of 165 family member (95 affected and 70 unaffected). The common clinical finding in affected individual included early-onet poterior perivacular retinal degeneration, vitreou degeneration, and retinal detachment. The incidence of retinal detachment wa 57% (95/165) and the mean age of onet wa 15.2 year. Orofacial, keletal, and auditory abnormalitie were een in 0%, 5%, and 7.5%, repectively, in a ubet of 28 affected ubject. Linkage to the collagen COL2A1 locu wa demontrated and a cytoine to adenoine tranition identified within exon 2, leading to the creation of a top codon at poition 86 (Cy86top). CONCLUION: Identification of the mutation in thi family enable diagnoi of individual at rik for potentially blinding complication in thi condition at an early age. Given the variability of the tickler phenotype, mutation detection allow for more comprehenive genetic couneling and direct clinical monitoring to family member inheriting the dieae gene.