The FBN1 gene provides instructions for making a large protein called fibrillin-1. This protein is transported out of cells into the extracellular matrix, which is an intricate lattice of proteins and other molecules that forms in the spaces between cells. In this matrix, fibrillin-1 binds to other molecules of fibrillin-1 and other proteins to form threadlike filaments called microfibrils. Microfibrils form elastic fibers, which enable the skin, ligaments, and blood vessels to stretch. Microfibrils also provide support to more rigid tissues such as those that support the nerves, muscles, and lenses of the eyes.
Microfibrils store a protein called transforming growth factor beta (TGF-β), a critical growth factor. TGF-β helps control the growth and division of cells, the process by which cells mature to carry out specific functions, cell movement, and the self-destruction of cells. Microfibrils help regulate the availability of TGF-β, which is turned off when stored in microfibrils and turned on when released.
Most of the mutations that cause Marfan syndrome change a single protein building block in the fibrillin-1 protein. The remaining FBN1 gene mutations result in an abnormal fibrillin-1 protein that cannot function properly. FBN1 gene mutations that cause Marfan syndrome reduce the amount of fibrillin-1 produced by the cell, alter the structure or stability of fibrillin-1, or impair the transport of fibrillin-1 out of the cell. These mutations lead to a severe reduction in the amount of fibrillin-1 available to form microfibrils. Without enough microfibrils, excess TGF-β growth factors are activated and elasticity in many tissues is decreased, leading to overgrowth and instability of tissues. Researchers have identified more than 1,000 FBN1 gene mutations that cause Marfan syndrome.
Patients with this disorder may be exceptionally tall, with long limbs
and long thin fingers. The most serious complication
is defects of the aortic valves. It may also affect the
lungs, eyes, and dural sac surrounding the spinal cord,
skeleton and hard plate.
DNA sequencing of the whole coding FBN1 gene mutation can detect approximately 70-93 % patients fulfilling Marfan syndrome diagnostic criteria.
Methodology: Sequencing of entire coding region
Purpose: Confirmation of Clinical Diagnosis
ICD-10 Code Q87.40
Test Requisition: Sequencing Requisition
CPT Code: 81408 Cost: $900.00
Turn-around-time: 5-6 weeks
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2. Collod-Béroud G, Boileau C. (2002) “Marfan syndrome in the third Millennium”. Eur J Hum Genet. 10(11):673-81. Review.
3. Mizuguchi T, Matsumoto N. (2007) “Recent progress in genetics of Marfan syndrome and Marfan-associated disorders”. J Hum Genet. 52(1):1-12.