Marfan syndrome (MFS) is an inherited connective-tissue disorder that occurs in one in 10,000 to one in 20,000 individuals caused by mutations in the gene encoding Fibrillin-1 (FBN1) a large molecule component of extracellular matrix. Individual affected by MFS show several clinical features of skeletal, cardiovascular and ocular (eye) system. The clinical features of skeletal system are increased height, disproportionately long bones and digits, joint laxity and vertebral column deformity (scoliosis). Moreover, people with this syndrome suffer from osteopenia, or poor bone mineralization. Aortic (large blood vessel) root dilatation, aortic regurgitation, heart mitral valve prolapsed and heart mitral regurgitation are the cardiovascular features. Eye defects such as myopia, corneal flatness and subluxation of the lenses (ectopia lentis) are present in MFS patients.
We have established human embryonic stem cells from a MFS embryo and human induced pluripotent stem cells (iPS) derived from the skin of Marfan patients. Analysis of these cell lines have unveiled unique features showing impaired ability to form bone, and all too readily formed cartilage. These aberrations mirror the most prominent clinical skeletal manifestation of the disease. Moreover, our research revealed that an alteration of Transforming Growth Factor  (TGF signaling is responsible for the pathological conditions observed. Importantly, this study demonstrated for the first time the faithful alignment of pathological features in cells obtained from both human embryonic stem cells and iPS cells providing complementary and powerful tools to gain further insights into human molecular pathogenesis, especially of MFS.