Nhung's research paper

Nhung Nguyen
March 13, 2009
Genetic pathway paper

Marfan syndrome

As a human being, we all desired to have a healthy physical appearance. Unfortunately, a small mutation, which changes in DNA sequence, could lead to severe genetic disorder. Those mutations usually occurred randomly and our body could not able to prevent it from happening. Marfan syndrome is known as a common genetic disorder of the connective tissue and can be passed down from parents to offspring. Since there is no definite cure for this type of disease, it is important to understand the caused and symptoms of this genetic pathway.

Marfan syndrome was first discovered in 1896 by a French doctor named Bernard Marfan (8). It was found to be an autosomal dominant connective tissue disorder that is highly expresses in the eye, skeleton, and the cardiovascular system (3). This inheritable disease can become severe overtime and could result in early death. The numbers of people who found to have Marfan syndrome in the United States is at least one out of 10,000 or one out of 25,000 people (5). The symptoms of this disease usually develop in a person’s first decade of life. About 50 percent of patients who have this syndrome have to go under aortic surgery, where a replacement of the aortic root is required (1, 13).

The cause of Marfan syndrome occurs by mutations in the Fibrillin (FBN1) gene on chromosome 15 (1, 7, 11). Fribillin is a multifunctional extracellular protein encoded by the FBN1 gene (4). FBN1 is a structural factor of the extracellular microfibril that impact physical properties to tissues (2). The size of FBN1 is about 237 kb and it is located on chromosome 15q21. It is composed of 65 exons, along with 3 more extra exons that merge together on the 5’ end (4). Each fibrillin monomer contains large number of epidermal growth factor-like motifs, which are capable of binding protein for transforming growth factor beta. The extracellular microfibril is about 10 to 14 nm in diameter. It function is to served as the scaffolding for deposition of tropoelastin to form elastic fibers (3). The gene that codes for fibrillin is codes for a protein that helps support the blood vessels, aorta, and body structures. Mutation, in the Fribillin gene leads to connective tissue disorder and therefore could affect the heart and arteries. It weakens the aorta wall under high pressure of stress (6)

People with Marfan syndrome tend to have the following symptoms: tall in size along with a thin body, long limbs, incompetence of the aortic valve or mitral valve, lens disorder and myopia, pectus deformities, and dural ectasia (1, 7). Pre-fibrillin consists of 2, 871 amino acids, and arranged into five distinct regions. About 75 % of the region is protein, which consists of numerous repeated cysteine-rich sequences homologous to the peptide motifs of the epidermal growth factor (EGF) and transforming growth factor –B binding protein (TGF-bp). Most of the repeated cysteine-rich are encoded by single exons (9). The mutation in fribillin leads to loss of function of the TGF-B signaling activity on extracellular formation (10).

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