PCR ASSAY CONFIRMS DIAGNOSIS IN SYNDROME WITH VARIABLY EXPRESSED PHENOTYPE - MUTATION DETECTION IN STICKLER SYNDROME

Stickler syndrome is an autosomal dominant disease with ocular (severe myopia, vitreal degeneration, and retinal detachment) and other syste mic manifestations (hearing loss, cleft palate, epiphyseal dysplasia, and premature osteoarthritis). As with other dominantly inherited cond itions, the clinical phenotype of Stickler syndrome varies considerabl y. To date, all mutations have been located in the type II procollagen (COL2A1) gene. Analysis of a C-->T mutation we had identified previou sly, in COL2A1 gene in exon 40, in a three generation pedigree showed the loss of a cleavage site for the TaqI restriction enzyme. Ne design ed a rapid PCR based restriction enzyme assay to detect this mutation and used it to establish the diagnosis in a neonate from the same pedi gree, presenting with the first occurrence of the Pierre-Robin sequenc e in the family and minimal ocular findings. These results underline t he potential diagnostic value of many as yet undetected DNA mutations in families affected with Stickler syndrome, since the variability of the phenotype can impede accurate diagnosis, appropriate genetic couns elling, and effective intervention and prophylactic treatment for affe cted people.