The FBLN5 gene provides instructions for making a protein called fibulin-5. This protein is part of a group of proteins called fibulins. Fibulins have a variety of functions in the extracellular matrix, which is the intricate lattice of proteins and other molecules that forms in the spaces between cells.
In the extracellular matrix, fibulin-5 appears to play a critical role in the assembly of elastic fibers. These slender bundles of proteins provide strength and flexibility to connective tissue (tissue that supports the body's joints and organs). Fibulin-5 is found in tissues and organs that are rich in elastic fibers, including developing arteries and the heart valves, lungs, and skin.
Health Conditions Related to Genetic Changes
At least four mutations in the FBLN5 gene have been identified in people with cutis laxa. Mutations in this gene can cause two different types of cutis laxa: an autosomal dominant form and an autosomal recessive form. In autosomal dominant cutis laxa, one copy of the altered FBLN5 gene in each cell is sufficient to cause the characteristic features of the disorder. In autosomal recessive cutis laxa, both copies of the gene in each cell must be altered to result in the disease.
The FBLN5 mutation known to cause autosomal dominant cutis laxa leads to the production of an abnormally long, nonfunctional version of fibulin-5. This abnormal protein interferes with the normal fibulin-5 produced from the other, unaltered copy of the FBLN5 gene. As a result, the amount of functional fibulin-5 in the extracellular matrix is severely reduced. A shortage of this protein prevents the assembly of elastic fibers, which weakens connective tissue in the skin, arteries, lungs, and other organs. These defects in connective tissue underlie the major features of cutis laxa.
Autosomal recessive cutis laxa results from FBLN5 mutations that change single protein building blocks (amino acids) in fibulin-5. These mutations alter the structure of the protein, trapping it within the cell. Because the defective fibulin-5 never makes it to the extracellular matrix, it is not available for the assembly of elastic fibers. A shortage of normal elastic fibers weakens connective tissue throughout the body, leading to the signs and symptoms of cutis laxa.More About This Health Condition
Age-related macular degeneration
MedlinePlus Genetics provides information about Age-related macular degenerationMore About This Health Condition
Researchers have been studying FBLN5 mutations as a possible risk factor for age-related macular degeneration, an eye disease that is a leading cause of vision loss among older people worldwide. Mutations in the FBLN5 gene have been found in a small number of people with age-related macular degeneration, but changes in this gene are probably not a major risk factor for this common eye disorder. A combination of genetic and environmental factors likely determine the risk of developing this disease.
Other Names for This Gene
- developmental arteries and neural crest epidermal growth factor-like
- urine p50 protein
Additional Information & Resources
Tests Listed in the Genetic Testing Registry
Scientific Articles on PubMed
Catalog of Genes and Diseases from OMIM
- Hu Q, Loeys BL, Coucke PJ, De Paepe A, Mecham RP, Choi J, Davis EC, Urban Z. Fibulin-5 mutations: mechanisms of impaired elastic fiber formation in recessive cutis laxa. Hum Mol Genet. 2006 Dec 1;15(23):3379-86. Epub 2006 Oct 11. Citation on PubMed
- Kobayashi N, Kostka G, Garbe JH, Keene DR, Bächinger HP, Hanisch FG, Markova D, Tsuda T, Timpl R, Chu ML, Sasaki T. A comparative analysis of the fibulin protein family. Biochemical characterization, binding interactions, and tissue localization. J Biol Chem. 2007 Apr 20;282(16):11805-16. Epub 2007 Feb 26. Citation on PubMed
- Loeys B, Van Maldergem L, Mortier G, Coucke P, Gerniers S, Naeyaert JM, De Paepe A. Homozygosity for a missense mutation in fibulin-5 (FBLN5) results in a severe form of cutis laxa. Hum Mol Genet. 2002 Sep 1;11(18):2113-8. Citation on PubMed
- Lotery AJ, Baas D, Ridley C, Jones RP, Klaver CC, Stone E, Nakamura T, Luff A, Griffiths H, Wang T, Bergen AA, Trump D. Reduced secretion of fibulin 5 in age-related macular degeneration and cutis laxa. Hum Mutat. 2006 Jun;27(6):568-74. Citation on PubMed or Free article on PubMed Central
- Markova D, Zou Y, Ringpfeil F, Sasaki T, Kostka G, Timpl R, Uitto J, Chu ML. Genetic heterogeneity of cutis laxa: a heterozygous tandem duplication within the fibulin-5 (FBLN5) gene. Am J Hum Genet. 2003 Apr;72(4):998-1004. Epub 2003 Feb 28. Citation on PubMed or Free article on PubMed Central
- Mullins RF, Olvera MA, Clark AF, Stone EM. Fibulin-5 distribution in human eyes: relevance to age-related macular degeneration. Exp Eye Res. 2007 Feb;84(2):378-80. Epub 2006 Nov 14. Citation on PubMed or Free article on PubMed Central
- Nonaka R, Onoue S, Wachi H, Sato F, Urban Z, Starcher BC, Seyama Y. DANCE/fibulin-5 promotes elastic fiber formation in a tropoelastin isoform-dependent manner. Clin Biochem. 2009 May;42(7-8):713-21. doi: 10.1016/j.clinbiochem.2008.12.020. Epub 2009 Jan 8. Citation on PubMed
- Stone EM, Braun TA, Russell SR, Kuehn MH, Lotery AJ, Moore PA, Eastman CG, Casavant TL, Sheffield VC. Missense variations in the fibulin 5 gene and age-related macular degeneration. N Engl J Med. 2004 Jul 22;351(4):346-53. Citation on PubMed
- Wachi H, Nonaka R, Sato F, Shibata-Sato K, Ishida M, Iketani S, Maeda I, Okamoto K, Urban Z, Onoue S, Seyama Y. Characterization of the molecular interaction between tropoelastin and DANCE/fibulin-5. J Biochem. 2008 May;143(5):633-9. doi: 10.1093/jb/mvn014. Epub 2008 Feb 10. Citation on PubMed