Focus was placed on the aorta, since aortic disease is life threatening in the Marfan syndrome and fibrillin-1 green fluorescence was most abundant in this tissue.
Furthermore, SMCs cannot generate force without connections to the extracellular matrix through focal adhesions, and mutations in the major protein in the extracellular matrix, fibrillin-1, linking SMCs to the matrix also cause thoracic aortic disease in individuals with Marfan syndrome.
We determined signs of descending aortic disease before disease onset in mice with a mutation in the fibrillin 1 gene (Fbn1(+/C1039G)), a validated mouse model of disease susceptibility and progression of aortic aneurysm of MFS.
This study shows that common genetic variants at 15q21.1 that probably act via FBN1 are associated with STAAD, suggesting a common pathogenesis of aortic disease in Marfan syndrome and STAAD.
In the probands with aortic diseases in young who cannot be diagnosed with MFS, mutations other than FBN1 mutations accounted for at least one-third of all causes of aortic disease.