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Genetics Home Reference: your guide to understanding genetic conditions
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FBN1

Reviewed March 2012

What is the official name of the FBN1 gene?

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.

What is the normal function of the FBN1 gene?

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.

How are changes in the FBN1 gene related to health conditions?

Marfan syndrome - caused by mutations in the FBN1 gene

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.

Weill-Marchesani syndrome - caused by mutations in the FBN1 gene

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.

other disorders - caused by mutations in the FBN1 gene

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.

Where is the FBN1 gene located?

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.

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.

Where can I find additional information about FBN1?

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.

What other names do people use for the FBN1 gene or gene products?

  • FBN
  • FBN1_HUMAN
  • fibrillin 1 (Marfan syndrome)
  • MFS1
  • SGS

See How are genetic conditions and genes named? (http://ghr.nlm.nih.gov/handbook/mutationsanddisorders/naming) in the Handbook.

What glossary definitions help with understanding FBN1?

amino acid ; aneurysm ; aorta ; apoptosis ; arachnodactyly ; cell ; connective tissue ; craniosynostosis ; differentiation ; disability ; 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).

References

  • Adès LC, Sullivan K, Biggin A, Haan EA, Brett M, Holman KJ, Dixon J, Robertson S, Holmes AD, Rogers J, Bennetts B. FBN1, TGFBR1, and the Marfan-craniosynostosis/mental retardation disorders revisited. Am J Med Genet A. 2006 May 15;140(10):1047-58. (http://www.ncbi.nlm.nih.gov/pubmed/16596670?dopt=Abstract)
  • Arbustini E, Grasso M, Ansaldi S, Malattia C, Pilotto A, Porcu E, Disabella E, Marziliano N, Pisani A, Lanzarini L, Mannarino S, Larizza D, Mosconi M, Antoniazzi E, Zoia MC, Meloni G, Magrassi L, Brega A, Bedeschi MF, Torrente I, Mari F, Tavazzi L. Identification of sixty-two novel and twelve known FBN1 mutations in eighty-one unrelated probands with Marfan syndrome and other fibrillinopathies. Hum Mutat. 2005 Nov;26(5):494. (http://www.ncbi.nlm.nih.gov/pubmed/16222657?dopt=Abstract)
  • Brautbar A, LeMaire SA, Franco LM, Coselli JS, Milewicz DM, Belmont JW. FBN1 mutations in patients with descending thoracic aortic dissections. Am J Med Genet A. 2010 Feb;152A(2):413-6. doi: 10.1002/ajmg.a.32856. (http://www.ncbi.nlm.nih.gov/pubmed/20082464?dopt=Abstract)
  • Collod-Béroud G, Boileau C. Marfan syndrome in the third Millennium. Eur J Hum Genet. 2002 Nov;10(11):673-81. Review. (http://www.ncbi.nlm.nih.gov/pubmed/12404097?dopt=Abstract)
  • Dietz HC, McIntosh I, Sakai LY, Corson GM, Chalberg SC, Pyeritz RE, Francomano CA. Four novel FBN1 mutations: significance for mutant transcript level and EGF-like domain calcium binding in the pathogenesis of Marfan syndrome. Genomics. 1993 Aug;17(2):468-75. (http://www.ncbi.nlm.nih.gov/pubmed/8406497?dopt=Abstract)
  • Faivre L, Collod-Beroud G, Loeys BL, Child A, Binquet C, Gautier E, Callewaert B, Arbustini E, Mayer K, Arslan-Kirchner M, Kiotsekoglou A, Comeglio P, Marziliano N, Dietz HC, Halliday D, Beroud C, Bonithon-Kopp C, Claustres M, Muti C, Plauchu H, Robinson PN, Adès LC, Biggin A, Benetts B, Brett M, Holman KJ, De Backer J, Coucke P, Francke U, De Paepe A, Jondeau G, Boileau C. Effect of mutation type and location on clinical outcome in 1,013 probands with Marfan syndrome or related phenotypes and FBN1 mutations: an international study. Am J Hum Genet. 2007 Sep;81(3):454-66. Epub 2007 Jul 25. (http://www.ncbi.nlm.nih.gov/pubmed/17701892?dopt=Abstract)
  • Faivre L, Gorlin RJ, Wirtz MK, Godfrey M, Dagoneau N, Samples JR, Le Merrer M, Collod-Beroud G, Boileau C, Munnich A, Cormier-Daire V. In frame fibrillin-1 gene deletion in autosomal dominant Weill-Marchesani syndrome. J Med Genet. 2003 Jan;40(1):34-6. (http://www.ncbi.nlm.nih.gov/pubmed/12525539?dopt=Abstract)
  • Glesby MJ, Pyeritz RE. Association of mitral valve prolapse and systemic abnormalities of connective tissue. A phenotypic continuum. JAMA. 1989 Jul 28;262(4):523-8. (http://www.ncbi.nlm.nih.gov/pubmed/2739055?dopt=Abstract)
  • Le Goff C, Mahaut C, Wang LW, Allali S, Abhyankar A, Jensen S, Zylberberg L, Collod-Beroud G, Bonnet D, Alanay Y, Brady AF, Cordier MP, Devriendt K, Genevieve D, Kiper PÖ, Kitoh H, Krakow D, Lynch SA, Le Merrer M, Mégarbane A, Mortier G, Odent S, Polak M, Rohrbach M, Sillence D, Stolte-Dijkstra I, Superti-Furga A, Rimoin DL, Topouchian V, Unger S, Zabel B, Bole-Feysot C, Nitschke P, Handford P, Casanova JL, Boileau C, Apte SS, Munnich A, Cormier-Daire V. Mutations in the TGFβ binding-protein-like domain 5 of FBN1 are responsible for acromicric and geleophysic dysplasias. Am J Hum Genet. 2011 Jul 15;89(1):7-14. doi: 10.1016/j.ajhg.2011.05.012. Epub 2011 Jun 16. (http://www.ncbi.nlm.nih.gov/pubmed/21683322?dopt=Abstract)
  • Loeys BL, Gerber EE, Riegert-Johnson D, Iqbal S, Whiteman P, McConnell V, Chillakuri CR, Macaya D, Coucke PJ, De Paepe A, Judge DP, Wigley F, Davis EC, Mardon HJ, Handford P, Keene DR, Sakai LY, Dietz HC. Mutations in fibrillin-1 cause congenital scleroderma: stiff skin syndrome. Sci Transl Med. 2010 Mar 17;2(23):23ra20. doi: 10.1126/scitranslmed.3000488. (http://www.ncbi.nlm.nih.gov/pubmed/20375004?dopt=Abstract)
  • Mizuguchi T, Matsumoto N. Recent progress in genetics of Marfan syndrome and Marfan-associated disorders. J Hum Genet. 2007;52(1):1-12. Epub 2006 Oct 24. Review. (http://www.ncbi.nlm.nih.gov/pubmed/17061023?dopt=Abstract)
  • NCBI Gene (http://www.ncbi.nlm.nih.gov/gene/2200)
  • Robinson PN, Arteaga-Solis E, Baldock C, Collod-Béroud G, Booms P, De Paepe A, Dietz HC, Guo G, Handford PA, Judge DP, Kielty CM, Loeys B, Milewicz DM, Ney A, Ramirez F, Reinhardt DP, Tiedemann K, Whiteman P, Godfrey M. The molecular genetics of Marfan syndrome and related disorders. J Med Genet. 2006 Oct;43(10):769-87. Epub 2006 Mar 29. Review. (http://www.ncbi.nlm.nih.gov/pubmed/16571647?dopt=Abstract)
  • Rommel K, Karck M, Haverich A, von Kodolitsch Y, Rybczynski M, Müller G, Singh KK, Schmidtke J, Arslan-Kirchner M. Identification of 29 novel and nine recurrent fibrillin-1 (FBN1) mutations and genotype-phenotype correlations in 76 patients with Marfan syndrome. Hum Mutat. 2005 Dec;26(6):529-39. (http://www.ncbi.nlm.nih.gov/pubmed/16220557?dopt=Abstract)

 

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.

 
Reviewed: March 2012
Published: September 15, 2014