Fibulin-2 exhibits high degree of variability, but no structural changes concordant with abdominal aortic aneurysms

We used conformation sensitive gel electrophoresis and direct sequencing of PCR products to screen for mutations in the cDNA for fibulin-2, an extrace llular matrix protein, from 11 patients with abdominal aortic aneurysms and two controls, When compared with the published reference sequence, a total of 14 single-base sequence variations were detected, Seven of the changes were neutral in that they did not result in an amino acid substitution, The re were five missense changes at sites not conserved between human and mous e, and two missense changes at sites conserved between human and mouse, All but two of the sequence variants studied were also present in an additiona l set of 102 control alleles analyzed, One of these two changes was a misse nse mutation, but it did not segregate with abdominal aortic aneurysms in t he family, whilst the other change was neutral, In conclusion, fibulin-2 ha s a large number of sequence variations in comparison with our previous ana lyses of type III collagen, and these variations will be useful in associat ion studies, There was an excellent overall agreement between direct sequen cing of PCR-products and conformation sensitive gel electrophoresis.