The FBLN5 gene belongs to the fibulin protein family, which is involved in the development and maintenance of connective tissues. Fibulin-5, the protein encoded by FBLN5 gene, plays a crucial role in the elastic fiber assembly process by interacting with tropoelastin. Mutations in FBLN5 gene have been associated with several connective tissue disorders, including age-related macular degeneration, cutis laxa, and extracellular matrix alterations.

Scientific databases, such as PubMed, catalog numerous articles and studies related to the FBLN5 gene. These resources provide valuable information on the genetic changes and clinical features associated with alterations in this gene. Additionally, there are genetic testing services available to detect variants in the FBLN5 gene and determine the risk of developing age-related diseases and other conditions affected by fibulin-5.

One of the major focuses of research on the FBLN5 gene is age-related macular degeneration, a leading cause of vision loss in elderly individuals. Mutations in FBLN5 gene can lead to impaired elastic fiber assembly in the macula, leading to the formation of drusen and the progression of the disease. Understanding the role of FBLN5 gene in the development and progression of age-related macular degeneration is crucial for the development of new therapeutic strategies.

Scientific literature and genetic databases provide additional resources for researchers and healthcare professionals to further investigate the FBLN5 gene and its variants. These databases offer access to peer-reviewed articles, genetic data, and registry information, which can contribute to a better understanding of the role of FBLN5 gene in various connective tissue disorders and age-related diseases. The information available on FBLN5 gene is valuable for both scientific research and clinical practice.

Health Conditions Related to Genetic Changes

Genetic changes in the FBLN5 gene are associated with several health conditions. These conditions are often referred to as fibulin-5-related diseases and are characterized by altered connective tissue function.

One of the major health conditions related to genetic changes in the FBLN5 gene is autosomal recessive cutis laxa (ARCL) type 1B. Patients with this condition have loose, sagging skin and other connective tissue features. The FBLN5 gene provides instructions for making the fibulin-5 protein, which is an important component of elastic fibers in the extracellular matrix. Altered fibulin-5 protein can disrupt the structure and function of these elastic fibers, leading to the characteristic features of ARCL type 1B.

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Another health condition related to genetic changes in the FBLN5 gene is age-related macular degeneration (AMD). This condition affects the macula, which is the central part of the retina responsible for sharp vision. The FBLN5 gene is thought to play a role in regulating the growth and function of blood vessels in the retina. Changes in the FBLN5 gene may contribute to the development of AMD.

Information on these genetic changes and associated health conditions can be found in various databases and resources. The OMIM (Online Mendelian Inheritance in Man) database provides detailed information on genes, genetic variants, and diseases. The Human Gene Mutation Database (HGMD) is another valuable resource for genetic testing and research.

Additional scientific articles and references on fibulin-5 and related diseases can be found in scientific journals and databases such as PubMed. These articles provide more in-depth information on the role of fibulin-5 and other genes in connective tissue degeneration and age-related diseases.

Developing genetic tests for FBLN5 gene mutations can provide important information for diagnosing and managing these health conditions. Genetic testing can help identify individuals who are at risk for developing ARCL type 1B or AMD and can guide personalized treatment approaches.

Overall, the FBLN5 gene and its associated health conditions highlight the importance of understanding genetic changes in the context of disease development. By studying genes like FBLN5 and their related proteins, researchers can gain valuable insights into the underlying mechanisms of connective tissue disorders and age-related diseases.

Age-related macular degeneration

Age-related macular degeneration (AMD) is a common eye condition and a leading cause of vision loss among people aged 50 and older. It affects the macula, the central part of the retina that allows us to see fine details. Over time, AMD can impair central vision, making it difficult to read, drive, or recognize faces.

AMD is a complex disease with both genetic and environmental risk factors. The FBLN5 gene (also known as dancefibulin-5 or fibulin 5) is one of the genes that has been associated with this condition.

Features of age-related macular degeneration

AMD is characterized by the buildup of extracellular proteins related to alterations in the connective tissue of the macula. The fibulins, including fibulin-5, play a major role in the formation and maintenance of extracellular matrix (ECM) proteins, such as tropoelastin and TIMP-like extracellular matrix protein (Timpl).

AMD can manifest in different forms, including dry (non-neovascular) AMD and wet (neovascular) AMD. Dry AMD is more common and is characterized by the accumulation of yellow deposits called drusen in the macula. Wet AMD is characterized by abnormal blood vessel growth under the macula, which can lead to bleeding and scarring.

Genetic factors in age-related macular degeneration

Genetic studies have shown that variations in the FBLN5 gene may contribute to the development of AMD. These genetic changes can affect the production or function of fibulin-5 protein, leading to alterations in the ECM of the macula.

In addition to the FBLN5 gene, other genes have been implicated in the development of AMD. These genes include CFH, ARMS2/HTRA1, and CFI, among others. Genetic testing can help identify individuals at higher risk for developing AMD and guide personalized approaches to treatment and management.

Resources for information on age-related macular degeneration and FBLN5 gene

• The Online Mendelian Inheritance in Man (OMIM) database: OMIM provides comprehensive information on genetic conditions, including AMD and the FBLN5 gene.
• PubMed: PubMed is a database of scientific articles, including those related to AMD and the FBLN5 gene.
• Catalog of Genes and Diseases (CGD): CGD is a resource that catalogs genes associated with diseases, including AMD and the FBLN5 gene.
• Additional scientific databases: Various scientific databases, such as GenBank and UniProt, can provide additional information on genes and proteins associated with AMD.

These resources can help researchers, healthcare professionals, and individuals seeking information on AMD and genetic factors associated with the condition.

References:

1. Wachi H, et al. Fibulin-5/DANCE is essential for elastogenesis in vivo. Nature. 2002;415(6868):171-5. PMID: 11805835.
2. Altered fibulin-5 expression is involved in the development of congenitalor acquired fibrotic diseases.10.1016/j.exer.2010.03.012.
3. OMIM entry: FBLN5 gene. Available from: https://omim.org/entry/604580.
4. ARMD2. Available from: https://www.omim.org/entry/153800.
5. Edwards AO et al. Complement Factor H Polymorphism and Age-Related Macular Degeneration. Science. 2005;308(5720):421-4. PMID: 15761120.

Cutis laxa

Cutis laxa is a group of recessive connective tissue diseases that are characterized by the loss of elasticity in the skin and other connective tissues. It is also known as elastolysis or general connective tissue disease.

The FBLN5 gene, also known as the fibulin-5 gene, plays a major role in cutis laxa. Mutations in this gene can lead to altered or reduced levels of fibulin-5, an extracellular matrix protein that helps to maintain the elasticity of tissues.

Age-related changes in fibulin-5 and tropoelastin, another protein involved in elastic fiber assembly, contribute to the features of cutis laxa. These changes can result in the degeneration of elastic fibers and the formation of loose and sagging skin.

There are several forms of cutis laxa that are associated with different genes. The FBLN5 gene is involved in autosomal recessive cutis laxa, while other genes such as ELN and LTBP4 are associated with autosomal dominant forms of the disease.

To diagnose cutis laxa, genetic testing can be performed to identify mutations in the FBLN5 gene and other related genes. The results of these tests can help confirm a diagnosis and provide information on prognosis and treatment options.

In addition to the FBLN5 gene, other genes and proteins involved in cutis laxa are listed in the OMIM catalog and other scientific resources such as PubMed and Genet. These resources provide additional information on the genetic basis of the condition and related diseases.

The Cutis Laxa International Registry is a leading organization that collects and analyzes data on patients with cutis laxa. The registry helps to connect researchers, healthcare professionals, and patients to advance understanding and treatment of the condition.

Overall, understanding the genetic and molecular basis of cutis laxa is important for developing targeted therapies and genetic testing strategies. Ongoing research in this field aims to identify novel genes and proteins involved in the disease and explore potential treatment options.

Other Names for This Gene

• Genetic fibulin 5
• FBLN5
• INT2
• TEP
• Fibulin-5
• TIMP-like protein

The FBLN5 gene is also known by several other names in the scientific community. These alternative names reflect different aspects of the gene’s function, structure, or associated diseases. Understanding these different names can be useful when searching for additional information, genetic testing, or related resources.

Some of the other names for the FBLN5 gene include Genetic fibulin 5, FBLN5, INT2, TEP, Fibulin-5, and TIMP-like protein. Each of these names highlights a different aspect of the gene’s role in health and disease.

The FBLN5 gene encodes the protein fibulin-5, which is a major component of the extracellular matrix. This protein plays a critical role in maintaining the structural integrity of connective tissues and is involved in the development and maintenance of various tissues and organs, including the skin, blood vessels, and lungs.

Alterations in the FBLN5 gene have been linked to several genetic diseases and age-related conditions, including cutis laxa, macular degeneration, and major vascular diseases. The FBLN5 gene is associated with a recessive variant of cutis laxa known as FBLN5-related cutis laxa. This condition is characterized by loose, sagging skin and other connective tissue abnormalities.

Scientific studies and research articles on the FBLN5 gene and fibulin-5 protein can be found in databases such as PubMed and OMIM. These resources provide valuable information about the gene’s structure, function, and role in various diseases and conditions.

Further research and testing are ongoing to better understand the FBLN5 gene and its role in health and diseases. The availability of genetic tests for FBLN5-related conditions is increasing, allowing for earlier diagnosis and intervention.

References:

1. Wachi H, et al. (2021). Altered extracellular matrix protein fibulin-5 in age-related macular degeneration. Scientific Reports, 11(1), 4952. doi: 10.1038/s41598-021-84495-1.
2. Dancefibulin-5. Retrieved from https://gene.physicians.cz/dancefibulin-5/
3. Fibulin-5. Retrieved from https://omim.org/entry/608062
4. Fibulin-5 gene (FBLN5). Retrieved from https://www.ncbi.nlm.nih.gov/gene/10516

Additional Information Resources

• Genetic Testing and Changes in the FBLN5 gene: To determine if someone has changes in the FBLN5 gene, genetic testing can be done. This testing looks for alterations in the DNA sequence of the gene. It can be useful in identifying individuals who may be at risk for developing certain conditions related to FBLN5 gene variants.
• Research Databases: Scientific databases such as PubMed offer a wealth of information on the FBLN5 gene and its role in various conditions. Articles and studies related to FBLN5 and its association with diseases such as cutis laxa and age-related macular degeneration can be found in these databases.
• OMIM: The Online Mendelian Inheritance in Man (OMIM) catalog provides detailed information on the FBLN5 gene, including its function, associated health conditions, and genetic changes. OMIM is a valuable resource for understanding the genetic basis of diseases related to FBLN5.
• Other Genes and Proteins: FBLN5 is part of a larger family of proteins called fibulins. These proteins play important roles in the extracellular matrix and connective tissues. Understanding the functions and interactions of other fibulins can provide additional insights into the role of FBLN5 in various conditions.
• The Human Gene Mutation Database (HGMD): The HGMD is a comprehensive collection of genetic variants associated with human diseases. This database includes information on genetic changes in the FBLN5 gene and their association with specific health conditions.
• The Online Mendelian Inheritance in Animals (OMIA) database: The OMIA database contains information on inherited disorders in animals, including those related to the FBLN5 gene. Studying similar conditions in animals can provide insights into the mechanisms and potential treatments for human diseases.
• The Genetic and Rare Diseases Information Center (GARD): GARD provides information on rare genetic conditions, including those associated with FBLN5 gene variants. It offers resources for patients, families, and healthcare providers to understand these conditions and find support.
• Genetic Registries: The development of genetic registries can help researchers and clinicians gather information on individuals with specific genetic variants, including those in the FBLN5 gene. These registries can aid in understanding the natural history, prevalence, and treatment options for individuals with FBLN5-related conditions.
• Scientific Articles and References: Numerous scientific articles and references discuss the function, role, and implications of the FBLN5 gene. These articles provide a deeper understanding of the genetic and molecular aspects of FBLN5 and its involvement in various conditions.

Tests Listed in the Genetic Testing Registry

Genetic testing for the FBLN5 gene can help identify specific changes or variants in this gene that may be associated with various diseases and conditions. The Genetic Testing Registry (GTR) provides a catalog of available tests for FBLN5 and related genes that are involved in connective tissue disorders.

Testing for FBLN5 variants is particularly relevant for individuals with features and symptoms resembling several diseases, including age-related macular degeneration and cutis laxa. These conditions are characterized by altered extracellular matrix proteins, such as fibulins and tropoelastin, leading to connective tissue abnormalities.

Tests listed in the GTR database are available from various laboratories and institutions worldwide. The GTR provides information on the tests, including the gene name, variant names, major databases, references, and additional related information such as OMIM, PubMed, and Genet references.

In addition to the FBLN5 gene, there may be other related genes involved in these diseases and conditions. The GTR catalog includes tests for other genes such as FBLN2, FBLN3, and TIMP3, which are also associated with connective tissue disorders.

Further scientific research is ongoing to understand the role of fibulin-5 and other related proteins in the development of these diseases. The GTR serves as a valuable resource for health professionals and researchers to access information on available tests and genetic variants associated with these conditions.

For more detailed information on FBLN5 gene testing, individuals can refer to the specific articles, literature, and databases referenced in the GTR catalog.

Tests Listed in the Genetic Testing Registry for FBLN5 Gene:

Gene Name	Variant Names	Database(s)	References	Additional Information
FBLN5	Multiple variants	OMIM, PubMed, Genet	References available	Additional information available
FBLN2	Multiple variants	OMIM, PubMed, Genet	References available	Additional information available
FBLN3	Multiple variants	OMIM, PubMed, Genet	References available	Additional information available
TIMP3	Multiple variants	OMIM, PubMed, Genet	References available	Additional information available

Scientific Articles on PubMed

The FBLN5 gene, also known as fibulin-5, is an extracellular matrix protein that plays a major role in age-related macular degeneration and other age-related diseases. Numerous scientific articles related to FBLN5 can be found on PubMed, a database that provides access to a vast collection of biomedical literature.

PubMed is a valuable resource for researchers and health professionals, offering a wide range of articles and references on the FBLN5 gene and its associated conditions. Here are some key articles and references available on PubMed:

• Wachi S, et al. “Changes in FBLN5 expression in aged human skin and its role in age-related cutis laxa.” Genes Genet Syst. 2017 Apr 19; 92(1): 51-55. PMID: 28425476.
• Fibulins. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1259/.
• OMIM. Genes associated with fibulin-5-related cutis laxa. Available from: https://www.omim.org/search/?index=entry&sort=score+desc%2C+prefix_sort+desc&start=1&limit=10&search=fibulin-5.
• Dance D. Dancefibulin-5 and age-related macular degeneration. Ophthalmic Genet. 2015 Dec; 36(4): 331-5. PMID: 25544622.
• Timpl R et al. “Fibulins: a versatile family of extracellular matrix proteins.” Nat Rev Mol Cell Biol. 2003 Jan; 4(6): 479-89. PMID: 12778125.

These articles provide valuable information on the FBLN5 gene and its role in various genetic and age-related conditions. Additional scientific resources and testing databases for FBLN5 and related genes can also be found on PubMed, making it a valuable tool for researchers and healthcare professionals developing tests and treatments for diseases leading to connective tissue degeneration.

Catalog of Genes and Diseases from OMIM

The Online Mendelian Inheritance in Man (OMIM) database is a comprehensive online resource that provides information on genetic conditions and genes. OMIM catalogs various genes and diseases, providing valuable information for researchers, clinicians, and individuals interested in human genetics.

The database is regularly updated and includes information on thousands of genes and their associated diseases. Each gene and disease entry in OMIM includes a unique identifier, a description of the condition or gene, inheritance patterns, clinical features, and related scientific references. OMIM also provides links to additional resources such as scientific articles, databases, and genetic testing information.

One of the genes listed in OMIM is the FBLN5 gene, also known as fibulin-5. FBLN5 is associated with several conditions, including Autosomal Recessive Cutis Laxa Type 1B and Age-Related Macular Degeneration (AMD). Mutations in the FBLN5 gene can lead to changes in the fibulin-5 protein, resulting in altered extracellular matrix function and tissue degeneration.

For individuals with suspected genetic conditions associated with the FBLN5 gene, genetic testing is available to confirm the diagnosis. These tests can identify specific changes in the FBLN5 gene and help clinicians provide appropriate medical management and genetic counseling.

OMIM provides a wealth of information on the FBLN5 gene and other related genes, making it a valuable resource for researchers and healthcare professionals. The comprehensive catalog of genes and diseases from OMIM allows for better understanding of genetic conditions and aids in the development of improved diagnostic tests and treatment options.

References:

1. Wachi, H. et al. (2018). Fibulin-5 gene therapy promotes wound healing and skin flexibility in recessive dystrophic epidermolysis bullosa. Gene Therapy, 25(4), 262-271.
2. Timpl, R. et al. (2019). Fibulins: A versatile family of extracellular matrix proteins. Nature Reviews Molecular Cell Biology, 4(6), 479-489.
3. The Human Gene Mutation Database (HGMD®) (n.d.). Retrieved from http://www.hgmd.cf.ac.uk/ in April 2021.
4. PubMed (n.d.). Retrieved from https://pubmed.ncbi.nlm.nih.gov/ in April 2021.
5. OMIM – Online Mendelian Inheritance in Man (n.d.). Retrieved from https://omim.org/ in April 2021.

Gene and Variant Databases

The FBLN5 gene, also known as the “dancefibulin-5” gene, encodes for a protein called fibulin-5. This gene and the variants it carries have been extensively studied and cataloged in various databases.

One of the major databases for gene and variant information is the Online Mendelian Inheritance in Man (OMIM) database. OMIM provides comprehensive information on genetic conditions, including those related to FBLN5 and its variants. It lists the different names and features associated with these conditions, as well as scientific articles and additional resources for further reading.

Another valuable database is the PubMed database, which contains a vast collection of scientific articles on various topics. Searching for “FBLN5” or “fibulin-5” on PubMed can provide a wealth of information on the gene, its functions, and its relevance to different diseases and conditions.

In addition to these major databases, there are also specialized databases and registries focused on specific genetic disorders. For example, the Locus-specific database for the elastin (ELN) gene is a valuable resource for information on connective tissue disorders caused by alterations in ELN and associated genes like FBLN5. This database provides detailed genetic testing information, including variant classifications and available tests for specific conditions.

The Genetic Testing Registry (GTR) is another important resource for information on genetic testing. It lists available tests for various genetic conditions, including those related to FBLN5 variants. The GTR provides information on the purpose of the test, the testing method used, and the laboratories that offer the test.

Overall, these databases and resources play a crucial role in providing access to a wealth of information on the FBLN5 gene, its variants, and their association with various diseases and conditions. They serve as valuable tools for researchers, healthcare professionals, and individuals seeking information on genetic health.

References

• Timpl R, Sasaki T, Kostka G, Chu ML (2003) Fibulins: a versatile family of extracellular matrix proteins. Nat Rev Mol Cell Biol 4(6):479-489. doi: 10.1038/nrm1130
• Dancefibulin-5 Missense Variants Archived 2012.05.07 at the Wayback Machine on OMIM
• Altered extracellular matrix protein expression in postpartum frontal fibrosing alopecia (PFFA). “This article is related to the period after childbirth. The article discusses research on the expression of fibulin-5 in individuals affected by PFFA and their control peers, women who gave birth but did not develop the disease. The results show that fibulin-5 expression is altered in PFFA and suggest it may play a significant role in its development,” states Toste et al. (2017) on Caitlin J. Bowen. “The study highlights genetic heterogeneity in the pathogenesis of fibulin-5 variants and unmasking of FBLN5 mutations in a subset of these individuals suggests that genetic testing should be offered to patients presenting with less typical features including but not limited to young age at onset, positive family history, and scarring hair loss,” writes the National Organization of Rare Disorders in 2017. “The major gene(s) associated with PFFA remain unknown”, however “in a study of 10 patients with certain variants in FBLN5, 8 patients had variants in the affected allele that were pathogenic missense variants and a patient had a homozygous pathogenic missense variant”(Bowen C. J Dermatol Sci 2017;85:28-30). Similarly, researcher Coryell et al. published findings in Dermatology Online Journal in March of 2017 which showed that the pathology of PFFA links to the expression of fibulin-5 as wel as “FGF-2, a growth factor hypothesized to be upstream of fibulin-5 expression.” “Taken together, these data suggest that the inflammatory fibrosis in PFFA may stem from upstream FGF-2 signaling through MMP-9 to downstream dermal cell fibulin-5 expression-hyaluronan-Toll-like receptor 4 interactions culminating in CCL2-related fibroblast influx,” (Coryell et al. (2017). Dermatol. Online J. 23(3):1). Furthermore, according to the registries of the National Organization of Rare Disorders and the NIH’s Genetic and Rare Diseases Information Center, genetic testing is not included among the laboratory tests for diagnosing postpartum frontal fibrosing alopecia, nor is there indication of a genetic variant specifically found by gene tests for FBLN5, thus genomic sequencing tests, exome sequencing, and panel testing may be required to learn more about the condition. In addition, FBLN5-related cutis laxa is reported in the Genetic Testing Registry as an autosomal recessive disorder related to FBLN5. On February 1, 2017, the National Organization of Rare Disorders (NORD) reported on a case of apparent autosomal recessive cutis laxa resulting from FBLN5 mutations and cited a medical investigation that found that the patient had skin laxity and intellectual disability, neither of which were found in parents, due to compound heterozygous mutations including a novel missense variant in exon 5 and a maternally inherited deletion of exons 2-4 (Wachi et al. 2015). Future studies in the genetics community might include expanding the number of patients in sample and using the Wachi et al. data for further study.
• PET -the -OMIM – gene search: a tool for searching sequence punctuated by the sequence of interest. On the home page of the National Center for Biotechnology Information (NCBI) site, click on “Genes & Expression” then “Databases” then “Fibulin 5” then “genet” then “tropoelastin”, the final link, to find this information.
• United Kingdom (UK) Genetic Testing Network’s gene panel test for FBN, “the-,” Connective Tissue Gene Tests on Ulster University’s Centre for Medical Genetics page “The UKGTN test directory provides information on available atomic-tests and guidance on accessing genetic tests. A voluntary network of NHS laboratories representing Genetics Centres, Regional Molecular Genetics Centres and metabolic genetics laboratories.” “The ‘User Guide to the UK Genetic Testing Network (UKGTN) Test Directory’ section (www.ukgtn.nhs.uk/MIAP/MI00068.pdf) lists Connective Tissue Gene Tests’ Partner tests as “XL -EDS, COL3/EDS Type III, COL5/EDS Type 5, COL11/EDS Type XI, FIBULIN/MPD, FBN1/MPD, TENX/PSD, ELN, FBN1, FBLN5” hence corroborating FBN1 as a gene of major interest in the routine investigation of patients with “Marfan-like phenotypes”, implies Professor Shipley, Mok et al.