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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, 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 (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.
Researchers have identified more than 1,000 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 protein building block (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.
A mutation in the FBN1 gene has also been identified in one family with Weill-Marchesani syndrome. This mutation 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.
FBN1 gene mutations have been found to cause a condition called acromicric dysplasia. This condition is characterized by severely short stature, short limbs, stiff joints, and distinctive facial features. It is unknown why the FBN1 gene mutations that cause Marfan syndrome result in tall stature while those that cause acromicric dysplasia lead to short stature.
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.
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 48,700,502 to 48,937,984
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 48,700,502 to base pair 48,937,984 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.
amino acid ; aneurysm ; aorta ; apoptosis ; arachnodactyly ; cell ; connective tissue ; craniosynostosis ; differentiation ; dislocation ; dysplasia ; ectopia lentis ; elastic ; extracellular ; extracellular matrix ; familial ; gene ; growth factor ; joint ; microfibrils ; mitral valve ; mutation ; proliferation ; protein ; short stature ; stature ; syndrome ; tissue
You may find definitions for these and many other terms in the Genetics Home Reference Glossary (http://www.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.