SEQUENCING OF CDNA FROM 50 UNRELATED PATIENTS REVEALS THAT MUTATIONS IN THE TRIPLE-HELICAL DOMAIN OF TYPE-III PROCOLLAGEN ARE AN INFREQUENTCAUSE OF AORTIC-ANEURYSMS

Detailed DNA sequencing of the triple-helical domain of type Ill proco llagen was carried out on cDNA prepared from 54 patients with aortic a neurysms. The 43 male and 11 female patients originated from 50 differ ent families and five different nationalities. 43 patients had at leas t one additional blood relative who had aneurysms. Five overlapping as ymmetric PCR products, covering all the coding sequences of the triple -helical domain of type III procollagen, were sequenced with 28 specif ic sequencing primers. Analysis of the sequencing gels revealed only t wo nucleotide changes that altered the structure of the protein. One w as a substitution of threonine for proline at amino acid position 501 and its functional importance was not clearly established. The other w as a substitution of arginine for an obligatory glycine at amino acid position 136. In 40 of the 54 patients, detection of a polymorphism in the mRNA established that both alleles were expressed. The results in dicate that mutations in type III procollagen are the cause of only ab out 2% of aortic aneurysms.