Fibrillin-1 is a protein that in humans is encoded by the FBN1gene, located on chromosome 15.[1][2]
FBN1 is a 230-kb gene with 65 coding exons that encode a 2,871-amino-acid long proprotein called profibrillin which is proteolytically cleaved near its C-terminus by the enzyme furin convertase to give fibrillin-1, a member of the fibrillin family, and the 140-amino-acid long protein hormone asprosin.[3][4]
Fibrillin-1 is a large, extracellular matrix glycoprotein that serves as a structural component of 10-12 nm calcium-binding microfibrils. These microfibrils provide force bearing structural support in elastic and nonelastic connective tissue throughout the body.
The FBN-1 gene is involved in a variety of embryonic developmental programs. The microfibrils that are made from fibrillin-1 contribute to both elastic and non-elastic structures. The formation of the elastic fibers in the heart valves and the aorta require the involvement of both FBN-1 and FBN-2.[6] It has been shown that both FBN-1 and FBN-2, along with the other components of elastic fibers, are expressed in the embryonic semilunar valves as early as 4 weeks of gestation.[7] These molecules interact to form the elastic fibers in the ventricularis layer of the semilunar valves. Fibrillin-1 and fibrillin-2 are also crucial for the development of elastic fibers in the aorta. While expression of fibrillin-2 decreases significantly after fetal development, the expression of fibrillin-1 continues into adulthood. This supports the idea that fibrilin-2 dictates the development of early elastic fibers, while fibrillin-1 provides the structural support of mature elastic fibers.[7]
When mutations in the FBN-1 or FBN-2 genes occur, significant deformations can result from the damage to the extracellular matrix. Marfan Syndrome is a congenital disease that arises from a mutation in the FBN-1 gene. This leads to the malformation and subsequent weakening of the microfibrils in the patient’s body, including the structures of the cardiovascular system. The weakened elastic fibers will result in an impaired durability and distensibility in the heart valves and aorta. This provides the explanation for the aortic aneurysms and prolapsed valves that are commonly associated with Marfan Syndrome.[8]
↑Romere C, Duerrschmid C, Bournat J, Constable P, Jain M, Xia F, Saha PK, Del Solar M, Zhu B, York B, Sarkar P, Rendon DA, Gaber MW, LeMaire SA, Coselli JS, Milewicz DM, Sutton VR, Butte NF, Moore DD, Chopra AR (April 2016). "Asprosin, a Fasting-Induced Glucogenic Protein Hormone". Cell. 165 (3): 566–79. doi:10.1016/j.cell.2016.02.063. PMID27087445.
↑Jacquinet A, Verloes A, Callewaert B, Coremans C, Coucke P, Paepe A, Kornak U, Lebrun F, Lombret J, Pierard GE, Robinson PN, Symoens S, Van Maldergem L, Debray FG (2014). "Neonatal progeroid variant of Marfan syndrome with congenital lipodystrophy results from mutations at the 3' end of FBN1 gene". Eur. J. Med. Genet. 57 (5): 230–234. doi:10.1016/j.ejmg.2014.02.012.
↑Ramachandra CJ, Mehta A, Guo KW, Wong P, Tan JL, Shim W (2015). "Molecular pathogenesis of Marfan syndrome". Int. J. Cardiol. 187: 585–91. doi:10.1016/j.ijcard.2015.03.423. PMID25863307.
↑Quondamatteo F; Reinhardt DP; Charbonneau NL; Pophal G; Sakai LY; Herken R (Dec 2002). "Fibrillin-1 and fibrillin-2 in human embryonic and early fetal development". Matrix Biology. 21 (8): 637-646.
↑ 7.07.1Votteler M; Berrio DA; Horke A; Sabatier L; Reinhardt DP; Nsair A; Aikawa E; Schenke-Layland K (June 2013). "Elastogenesis at the onset of human cardiac valve development". Development. 140: 2345-2353. doi:10.1242/dev.093500. PMID23637335.
↑Ammash, MD, Naser M.; Sundt, MD, Thoralf M.; Connolly, MD, Heidi M. (January 2008). "Marfan Syndrome—Diagnosis and Management". Current Problems in Cardiology. 33 (1): 7-39.
Handford PA (Dec 2000). "Fibrillin-1, a calcium binding protein of extracellular matrix". Biochimica et Biophysica Acta. 1498 (2–3): 84–90. doi:10.1016/s0167-4889(00)00085-9. PMID11108952.
Robinson PN, Booms P, Katzke S, Ladewig M, Neumann L, Palz M, Pregla R, Tiecke F, Rosenberg T (Sep 2002). "Mutations of FBN1 and genotype-phenotype correlations in Marfan syndrome and related fibrillinopathies". Human Mutation. 20 (3): 153–61. doi:10.1002/humu.10113. PMID12203987.
Adès LC, Holman KJ, Brett MS, Edwards MJ, Bennetts B (Apr 2004). "Ectopia lentis phenotypes and the FBN1 gene". American Journal of Medical Genetics Part A. 126A (3): 284–9. doi:10.1002/ajmg.a.20605. PMID15054843.
