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The official name of this gene is “fibrillin 1.”
FBN1 is the gene's official symbol. The FBN1 gene is also known by other names, listed below.
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, molecules of fibrillin-1 attach (bind) to each other and to 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 bones and the tissues 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 affects development by helping to control the growth and division (proliferation) of cells, the process by which cells mature to carry out specific functions (differentiation), cell movement (motility), and the self-destruction of cells (apoptosis). Microfibrils help regulate the availability of TGF-β, which is turned off (inactivated) when stored in microfibrils and turned on (activated) when released.
At least nine FBN1 gene mutations have been identified in people with acromicric dysplasia. This condition is characterized by severely short stature, short limbs, stiff joints, and distinctive facial features.
FBN1 gene mutations that cause acromicric dysplasia are located in an area of the gene called exons 41 and 42, and change single protein building blocks (amino acids) in a region of the fibrillin-1 protein called TGF-β binding-protein-like domain 5. The mutations result in a reduction and disorganization of the microfibrils. Without enough normal microfibrils to store TGF-β, the growth factor is abnormally active. These effects likely contribute to the physical abnormalities that occur in acromicric dysplasia, but the mechanisms are unclear.
It is unknown why the FBN1 gene mutations that cause acromicric dysplasia lead to short stature, while certain other FBN1 gene mutations that also increase TGF-β activity cause a disorder called Marfan syndrome (see below), which is characterized by tall stature.
Researchers have identified more than 1,300 FBN1 gene mutations that cause Marfan syndrome, a disorder that affects the connective tissue supporting the body's joints and organs. Abnormalities in the connective tissue lead to heart and eye problems in people with this disorder. In addition, affected individuals are usually tall and slender with elongated fingers and toes and other skeletal abnormalities. Most of the mutations that cause Marfan syndrome change a single amino acid 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 and the signs and symptoms of Marfan syndrome.
Mutations in the FBN1 gene have also been identified in Weill-Marchesani syndrome. One of the identified mutations deletes part of the gene, leading to the production of an unstable version of the fibrillin-1 protein. The unstable protein likely interferes with the assembly of microfibrils. Abnormal microfibrils weaken connective tissue, which causes the eye, heart, and skeletal abnormalities associated with Weill-Marchesani syndrome.
Some FBN1 gene mutations cause a disorder called isolated ectopia lentis, in which dislocation of the lens of the eye causes vision problems. There are no other signs or symptoms associated with isolated ectopia lentis, which usually begins in adulthood.
Mutations in the FBN1 gene can also cause a condition called stiff skin syndrome. This condition is characterized by very hard, thick skin covering most of the body. The abnormal skin limits movement and can lead to joint deformities called contractures that restrict the movement of certain joints. The signs and symptoms of stiff skin syndrome usually become apparent in infancy to mid-childhood.
Mutations in the FBN1 gene can cause another condition called MASS syndrome. This condition involves abnormalities in several parts of the body, including the mitral valve (one of the valves that controls blood flow through the heart), the aorta (a large blood vessel that distributes blood from the heart to the rest of the body), the skeleton, and the skin.
FBN1 gene mutations may be involved in a disorder known as Shprintzen-Goldberg syndrome, which is typically apparent in infancy. The features of this syndrome are variable, but the main characteristics include premature fusion of certain bones of the skull (craniosynostosis) that affects the shape of the head and face; distinctive facial features; long, slender fingers and toes (arachnodactyly) and other skeletal abnormalities; and intellectual disability.
Geleophysic dysplasia, a disorder similar to acromicric dysplasia (described above) but more severe, with the addition of cardiovascular and respiratory problems, can also be caused by FBN1 gene mutations. As in acromicric dysplasia, the FBN1 gene mutations that cause geleophysic dysplasia are located in exon 41 or 42.
Mutations in the FBN1 gene have also been associated with familial thoracic aortic aneurysm and dissection (familial TAAD). This disorder involves problems with the aorta, which is the large blood vessel that distributes blood from the heart to the rest of the body. The upper part of the aorta (the thoracic aorta) can become weakened and stretched, causing a bulge in the blood vessel wall (an aneurysm) or a sudden tearing of the layers in the aorta wall (aortic dissection). People with mutations in the gene inherit an increased risk of thoracic aortic aneurysms and dissection, not the conditions themselves.
It is unknown why different mutations in the FBN1 gene cause such a variety of disorders.
Cytogenetic Location: 15q21.1
Molecular Location on chromosome 15: base pairs 48,408,305 to 48,645,787
The FBN1 gene is located on the long (q) arm of chromosome 15 at position 21.1.
More precisely, the FBN1 gene is located from base pair 48,408,305 to base pair 48,645,787 on chromosome 15.
See How do geneticists indicate the location of a gene? (http://ghr.nlm.nih.gov/handbook/howgeneswork/genelocation) in the Handbook.
You and your healthcare professional may find the following resources about FBN1 helpful.
You may also be interested in these resources, which are designed for genetics professionals and researchers.
See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.
acids ; amino acid ; aneurysm ; aorta ; aortic dissection ; apoptosis ; arachnodactyly ; cardiovascular ; cell ; connective tissue ; craniosynostosis ; differentiation ; disability ; dislocation ; domain ; dysplasia ; elastic ; exon ; extracellular ; extracellular matrix ; familial ; gene ; growth factor ; inherit ; joint ; microfibrils ; mitral valve ; proliferation ; protein ; respiratory ; short stature ; stature ; syndrome ; tissue
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://ghr.nlm.nih.gov/glossary).
The resources on this site should not be used as a substitute for professional medical care or advice. Users seeking information about a personal genetic disease, syndrome, or condition should consult with a qualified healthcare professional. See How can I find a genetics professional in my area? (http://ghr.nlm.nih.gov/handbook/consult/findingprofessional) in the Handbook.