SINGLE BASE MUTATION THAT SUBSTITUTES GLUTAMIC-ACID FOR GLYCINE-1021 IN THE COL3A1 GENE AND CAUSES EHLERS-DANLOS SYNDROME TYPE-IV

The proposita described here was a 24-year-old woman with an acrogeric form of the Ehlers-Danlos syndrome including a massive dissecting aor tic aneurysm. She was found to have a single-base mutation that substi tuted glutamic acid for glycine at amino acid position 1021 in the tri ple-helical domain of the type III procollagen. It is the most carboxy -terminal single-base mutation characterized to date in the COL3A1 gen e. Analysis of medium and cell layer proteins from proposita's culture d skin fibroblasts showed that the mutant protein was poorly secreted, migrated more slowly on a polyacrylamide gel, and was partially unsta ble at +25-degrees-C to brief digestion with trypsin.