The defect in Marfan syndrome

Article Abstract:

Marfan syndrome is an inherited disorder that affects several different parts of the body. Patients with Marfan syndrome are likely to have disproportionately long arms, legs, and fingers. Patients are also prone to have dislocated lenses in their eyes. There is also a defect in the aorta, and this major blood vessel may suddenly burst, which can be fatal. It is estimated that about 1 in 10,000 people have Marfan syndrome. Although it was widely suspected that some defect in a connective tissue protein was responsible, for many years researchers had been unable to find the genetic defect responsible for this syndrome. However, in the July 25, 1991 issue of the journal Nature, three different research groups report their findings on genes that seem to be responsible for Marfan syndrome and some related conditions. This most recent gene research began in earnest when a new connective tissue protein was identified in 1986. Dubbed 'fibrillin', it occurred in the same tissues that were most affected by the syndrome. Both Marfan syndrome and the fibrillin gene were found to be located on the long arm of chromosome 15 (15q), and efforts began to sequence the gene and identify a mutation that might cause the disorder. It has now been found that there are, in fact, two closely-related fibrillin genes, FBN1 and FBN2. FBN2 is located on chromosome 5, and one of the research groups has found that while mutations of FBN1 may be responsible for Marfan syndrome, mutations of FBN2 may be responsible for congenital contractural arachnodactyly (CCA). The symptoms of CCA are similar to Marfan syndrome, but the conditions may be distinguished by careful examination. (Consumer Summary produced by Reliance Medical Information, Inc.)

---

Partial sequence of a candidate gene for the Marfan syndrome

Article Abstract:

Fibrillin is a recently discovered protein that is a component of microfibrils, ubiquitous structures found in connective tissue. Parts of the body in which these microfibrils are found include the ligaments that suspend the lens in the eye and in the elastic fibers of the blood vessel walls. Since both the lenses and the blood vessel walls are affected in the genetic disorder Marfan syndrome, fibrillin became a prime suspect for the underlying cause of this disorder. Studies of patients and their families have previously shown that the Marfan syndrome gene is located on the long arm of chromosome 15. Techniques of molecular biology have been used to demonstrate that the fibrillin gene is also located on chromosome 15, specifically at 15q21.1. Now that the gene for fibrillin has been located precisely, it is possible to clone this gene; by inserting it into microorganisms, large quantities of the human fibrillin gene DNA for genetic sequencing and study can be obtained. In an accompanying report, the DNA sequencing data from the fibrillin gene from two Marfan syndrome patients are analyzed. These data show that Marfan syndrome may be the result of a missense mutation. A missense mutation results in the substitution of one amino acid for different amino acid in the protein that is synthesized. Although fibrillin is a large protein with molecular weight of about 350,000, the change in a single amino acid may result in a change in the shape of the fibrillin molecule. This change in shape, or conformation, may alter the function of the fibrillin, and ultimately result in the connective tissue abnormalities of Marfan syndrome. (Consumer Summary produced by Reliance Medical Information, Inc.)

---

Linkage of Marfan syndrome and a phenotypically related disorder to two different fibrillin genes

Article Abstract:

Marfan syndrome is an inherited disorder of connective tissue. The condition may affect the eyes and the growth of the bones, which may end up being disproportionately long. The condition also affects elastic tissue within the arteries, and patients with Marfan syndrome often die prematurely due to cardiovascular complications. In some cases, young patients with Marfan syndrome die suddenly when their aorta bursts or the wall of the aorta dissects. The diagnosis of Marfan syndrome is based only upon signs and symptoms, since the underlying genetic defect is not known. Evidence has now been found, however, to implicate the protein fibrillin as a cause of Marfan syndrome. Fibrillin is a connective tissue protein found in the same tissues affected by Marfan syndrome. A gene for fibrillin, FBN1, has been located on the long arm of chromosome 15, specifically 15q15-21. The gene for Marfan syndrome has been localized to the same region, providing a strong indication that the fibrillin gene and the Marfan syndrome gene may be the same. At the same time the fibrillin gene was found on chromosome 15, a second fibrillin gene, FNB2, was found on chromosome 5, specifically 5q23-31. This second fibrillin gene has been linked to the genetic location of the gene for congenital contractural arachnodactyly, a disease that is distinct from Marfan syndrome, but with very similar symptoms. The fact that two different disorders with similar symptoms are linked to two different fibrillin genes provides very strong evidence to suggest that abnormalities of fibrillin are responsible for these connective tissue disorders. (Consumer Summary produced by Reliance Medical Information, Inc.)

Similar abstracts:

• Abstracts: Effects of light and presence of fish on lure display and larval release behaviours in two species of freshwater mussels
• Abstracts: The Toll-like receptor is recruited to machrophage phagosomes and discriminates between pathogens. The innate immune response to bacterial flagellin is mediated by Toll-like receptor 5
• Abstracts: Amphibian declines and environmental change: Use of remote-sensing data to identify environmental correlates. part 2
• Abstracts: Amphibian declines and environmental change: Use of remote-sensing data to identify environmental correlates. Evaluating ultraviolet radiation exposure with satellite data at sites of amphibian declines in Central and South America
• Abstracts: Mast cells as a source of both preformed and immunologically inducible TNF-alpha/cachectin. Mast cells promote homeostasis by limiting endothelin-1-induced toxicity

This website is not affiliated with document authors or copyright owners. This page is provided for informational purposes only. Unintentional errors are possible.