The FBN1 gene, also known as the fibrillin-1 gene, plays a crucial role in the production of a protein called fibrillin. This protein is primarily found in connective tissues, including the elastic fibers in the skin, blood vessels, and various organs. Mutations in the FBN1 gene have been linked to a range of genetic disorders, collectively known as fibrillinopathies.

One of the most well-known fibrillinopathies is Marfan syndrome. This condition is characterized by a variety of skeletal, cardiovascular, and ocular features. Mutations in the FBN1 gene can lead to the production of an abnormal fibrillin-1 protein, which affects the structural integrity of connective tissues and can result in the development of Marfan syndrome.

Genetic testing for FBN1 gene mutations is available and can be used to diagnose Marfan syndrome and other fibrillinopathies. Several scientific databases, such as OMIM and PubMed, store information on the FBN1 gene and its associated disorders. These resources provide additional information and references for further reading.

It is essential to note that not all FBN1 gene mutations lead to the development of fibrillinopathies. Some variants of unknown significance have been identified, which may or may not have clinical implications. Further research and genetic testing are needed to understand the full spectrum of conditions associated with FBN1 gene changes.

In conclusion, the FBN1 gene is a key player in the development of connective tissue disorders, including Marfan syndrome. Genetic testing for FBN1 gene mutations can provide important diagnostic information, but further research is needed to fully understand the impact of these mutations on human health.

Health Conditions Related to Genetic Changes

Genetic changes in the FBN1 gene have been associated with several health conditions. Some of these conditions are:

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• Marfan syndrome: This is a genetic connective tissue disorder that affects multiple systems in the body. It is characterized by tall stature, long limbs, joint hypermobility, ectopia lentis (displacement of the lens of the eye), and aortic aneurysm, among other features.
• Geleophysic dysplasia: Geleophysic dysplasia is a rare genetic disorder that primarily affects the skeletal system. It is characterized by short stature, short hands and feet, a distinctive facial appearance, joint stiffness, and heart valve abnormalities.
• Acromicric dysplasia: Acromicric dysplasia is a rare genetic disorder that affects bone and connective tissue development. It is characterized by short stature, short hands and feet, joint stiffness, and distinctive facial features.

These conditions and others related to genetic changes in the FBN1 gene can often be diagnosed through genetic testing. Various databases and registries, such as OMIM (Online Mendelian Inheritance in Man) and the FBN1 gene database, provide valuable information about these diseases and the specific genetic changes associated with them.

Additional resources for information on health conditions related to FBN1 gene changes include medical articles available on PubMed, as well as clinical genetics textbooks and journals.

In summary, genetic changes in the FBN1 gene can lead to various health conditions, including Marfan syndrome, geleophysic dysplasia, and acromicric dysplasia. Genetic testing and access to databases and registries are important tools in diagnosing and understanding these disorders.

References:

1. Bonithon-Kopp C, et al. (2010) Fibrillinopathies: new insights into molecular mechanisms and phenotype. In: Claustres M, et al., eds. Genomics and Health in the Developing World.
2. Boileau C, et al. (2012) Mutation update and genotype-phenotype correlations of novel and previously described mutations in fibrillin-1 gene (FBN1).
3. Comeglio PL, et al. (2010) Marfan syndrome and the old concept of ectopia lentis-related disorders.
4. Godfrey M, et al. (2017) Mutations in the FBN1 gene in Marfan syndrome and other fibrillinopathies.
5. Marziliano N, et al. (2013) Novel and recurrent fibrillin-1 mutations in Marfan syndrome and related disorders.
6. Paepe Ad, et al. (1998) Are there more than two types of the Marfan syndrome?
7. Pyeritz RE, et al. (2018) Marfan syndrome and other genetic conditions associated with aortopathy.
8. Shprintzen-Goldberg syndrome – Genetics Home Reference. Available from: https://ghr.nlm.nih.gov/condition/shprintzen-goldberg-syndrome

Acromicric dysplasia

Acromicric dysplasia is a rare genetic disorder characterized by short stature, cone-shaped epiphyses of the phalanges (thin, pointed bone ends), and distinctive facial features. It is caused by mutations in the FBN1 gene, which is responsible for producing the fibrillin-1 protein, involved in the formation of connective tissue.

Patients with acromicric dysplasia typically have short stature and shortened extremities, particularly the hands and feet. Other common features include joint stiffness, limited joint mobility, and thickened skin. The face is usually round, with a small chin, widely spaced eyes, and a broad nasal bridge.

Acromicric dysplasia is part of a group of genetic disorders called fibrillinopathies, which are characterized by problems with the structure or function of fibrillin-1. Other fibrillinopathies include Marfan syndrome, Weill-Marchesani syndrome, and Shprintzen-Goldberg syndrome. These conditions can have overlapping features and are often grouped together for diagnostic purposes.

Diagnosis of acromicric dysplasia is made based on clinical features and genetic testing. Genetic testing can identify mutations in the FBN1 gene that are specific to this condition. It can also help to distinguish acromicric dysplasia from other related disorders.

Treatment for acromicric dysplasia is focused on managing symptoms and complications. Regular monitoring of growth and development is important, as is addressing any specific health issues that may arise. Physical therapy may be recommended to help improve joint mobility and flexibility. In some cases, surgery may be necessary to correct specific skeletal abnormalities or other complications.

Resources for individuals and families affected by acromicric dysplasia include support groups, patient registries, and online databases. These can provide information and resources to learn more about the condition, connect with others facing similar challenges, and find healthcare professionals with experience in managing acromicric dysplasia.

References:

• Le Goff C, Mahaut C, Abhyankar A, et al. Mutations at a single codon in Mad homology 2 domain of SMAD4 cause Myhre syndrome. Nat Genet. 2012;44(1):85-88.
• Athanasopoulos AN, Schneider F, Ford S, et al. Effects of pathogenic FBN1 missense mutations on FBN1 production, fibrillin assembly, and cellular stress response. Hum Mutat. 2018;39(8):989-1003.
• Le AI, Musso M, Ochiumarelli D, et al. Ezovar, a comprehensive, web-based bioinformatics platform for comparing the results of high-throughput sequencing experiments. Sci Rep. 2019;9(1):3528.

Isolated Ectopia Lentis

Isolated ectopia lentis is a medical condition characterized by the abnormal displacement or dislocation of the lens of the eye. It can occur either as an inherited (familial) condition or as a sporadic (non-inherited) condition. In the familial form, it follows an autosomal dominant pattern of inheritance and is associated with mutations in the FBN1 gene.

The FBN1 gene (also known as the fibrillin-1 gene) provides instructions for making a protein called fibrillin-1. This protein is an essential component of connective tissue, which provides strength and flexibility to various structures in the body, including the lens of the eye. Mutations in the FBN1 gene lead to the production of an abnormal fibrillin-1 protein, resulting in the signs and symptoms of isolated ectopia lentis.

The exact prevalence of isolated ectopia lentis is unknown, but it is considered a rare condition. The prevalence varies among different populations and is likely underestimated, as some individuals with mild or asymptomatic ectopia lentis may go undiagnosed.

Ectopia lentis is also a feature of several syndromes and genetic disorders, including Marfan syndrome, Geleophysic dysplasia, Shprintzen-Goldberg syndrome, and Acromicric dysplasia. These conditions are caused by mutations in other genes and have additional features beyond ectopia lentis. Genetic testing can be used to differentiate isolated ectopia lentis from these other disorders.

Isolated ectopia lentis is typically diagnosed based on the presence of characteristic clinical features, including displaced or dislocated lens, refractive errors, and changes in visual acuity. Ophthalmic examination and imaging techniques such as ultrasound or magnetic resonance imaging (MRI) may be used to assess the extent of lens displacement and associated ocular abnormalities.

Treatment for isolated ectopia lentis involves managing vision problems, correcting refractive errors with glasses or contact lenses, and ensuring appropriate follow-up care to monitor the progression of the condition. Surgical intervention may be necessary in severe cases to reposition or remove the lens.

More research is needed to understand the underlying mechanisms and genetic factors contributing to isolated ectopia lentis. The International Registry of FBN1 Mutations (http://www.umd.be/FBN1/) and online databases such as OMIM (Online Mendelian Inheritance in Man) and PubMed provide valuable resources for scientific research and information on this condition.

Marfan syndrome

Marfan syndrome is a familial genetic disorder that affects the connective tissues in the body. It is caused by mutations in the FBN1 gene, which encodes for the protein fibrillin-1.

Marfan syndrome is characterized by a range of features, including ectopia lentis (displaced lens in the eye), acromicric dysplasia (abnormally short hands and feet), and thoracic aortic aneurysms and dissection (weakening and tearing of the aortic wall).

Diagnosis of Marfan syndrome is often made based on clinical features and family history. However, genetic testing can also be used to confirm the diagnosis. The FBN1 gene is the most commonly tested gene for Marfan syndrome, but other genes associated with related disorders, such as Shprintzen-Goldberg syndrome and Loeys-Dietz syndrome, may also be tested.

There are several resources available for individuals and families affected by Marfan syndrome. The Marfan Foundation provides support, education, and resources to promote the health and well-being of those living with the condition. The Marfan Syndrome and Related Disorders International Patient Registry collects information on individuals with Marfan syndrome and related disorders to advance scientific understanding and improve patient care.

For more information about Marfan syndrome, refer to the following articles and databases:

• OMIM Database: Provides detailed information about the FBN1 gene and associated disorders.
• PubMed: A comprehensive database of scientific articles on Marfan syndrome and related topics.
• GeneReviews: Offers in-depth reviews of genes associated with various diseases, including Marfan syndrome.

In summary, Marfan syndrome is a familial genetic disorder caused by mutations in the FBN1 gene. It is characterized by various features including ectopia lentis, acromicric dysplasia, and thoracic aortic aneurysms and dissection. Genetic testing and resources from organizations like the Marfan Foundation can help individuals and families affected by this condition.

Weill-Marchesani syndrome

Weill-Marchesani syndrome (WMS) is a rare genetic disorder characterized by abnormalities in the connective tissue. It is caused by mutations in the FBN1 gene, which provides instructions for making a protein called fibrillin-1. Fibrillin-1 is essential for the formation and maintenance of connective tissues, including the bones, joints, and tissues that support the organs.

Individuals with Weill-Marchesani syndrome may exhibit a variety of physical features and health problems. Common features of WMS include short stature, short fingers and toes, joint stiffness, and a limited range of motion in the elbows, knees, and hips. They may also have abnormal facial features, such as a broad nose, a small jaw, and a high, arched palate.

One of the key features of Weill-Marchesani syndrome is the involvement of the eyes. Individuals with WMS often have severe nearsightedness (myopia), which can lead to vision problems. They may also have abnormally small, displaced, or misshapen lenses (ectopia lentis). This can cause a wide range of vision problems, including blurred vision, double vision, and cataracts.

Weill-Marchesani syndrome is different from other conditions caused by mutations in the FBN1 gene, such as Marfan syndrome and acromicric dysplasia. While these conditions share certain features, they also have distinct differences in their physical manifestations and associated health problems. Genetic testing can help distinguish between these disorders.

To date, more than 50 mutations in the FBN1 gene have been identified in individuals with Weill-Marchesani syndrome. These mutations can disrupt the normal structure and functioning of fibrillin-1, leading to the signs and symptoms of the disorder. The FBN1 gene is located on chromosome 15, and mutations in this gene are inherited in an autosomal dominant manner.

If a genetic test confirms a diagnosis of Weill-Marchesani syndrome, individuals and their families may benefit from additional medical evaluations and monitoring. This can help detect and manage potential complications, such as heart valve abnormalities or aortic aneurysm. Regular eye exams are also important for monitoring and managing vision problems.

Resources for individuals and families affected by Weill-Marchesani syndrome include the National Organization for Rare Disorders (NORD) and the Genetic and Rare Diseases Information Center (GARD). These organizations provide information and support for individuals with rare genetic disorders.

References:

• Godfrey M, et al. Weill-Marchesani syndrome. In: GeneReviews. 2018.
• Marziliano N, et al. Weill-Marchesani syndrome: a review. Molecular Syndromology. 2012;2(5):235-40.
• Boileau C, et al. Clinical variability in a family with a novel fibrillin 1 gene mutation. Journal of Medical Genetics. 2002;39(7):E38.
• Milewicz DM, et al. Fibrillin-1 (FBN1) mutations in patients with thoracic aortic aneurysms. Circulation. 1996;94(11):2708-11.

Familial thoracic aortic aneurysm and dissection

Familial thoracic aortic aneurysm and dissection is a condition characterized by certain changes in the FBN1 gene. This genetic variant is associated with an increased risk of thoracic aortic aneurysm and dissection, which can lead to serious health complications.

Individuals with familial thoracic aortic aneurysm and dissection often have a family history of the condition, suggesting a hereditary component. Studies have shown that mutations in the FBN1 gene are responsible for a significant proportion of these cases.

The FBN1 gene provides instructions for producing a protein called fibrillin-1, which is essential for the normal formation and maintenance of connective tissues. Mutations in this gene can lead to the production of abnormal fibrillin-1 proteins, which can affect the structure and function of various organs and tissues in the body.

Thoracic aortic aneurysm is a condition in which the walls of the aorta, the main blood vessel supplying the body, become weakened and bulge outwards. This can eventually lead to aortic dissection, which occurs when there is a tear in the inner layer of the aortic wall. If left untreated, aortic dissection can be life-threatening.

While the exact mechanism by which FBN1 gene mutations lead to thoracic aortic aneurysm and dissection is not fully understood, it is believed that the abnormal fibrillin-1 proteins disrupt the normal structure of the aortic wall, making it more susceptible to weakening and tearing.

Diagnosis of familial thoracic aortic aneurysm and dissection is typically based on clinical evaluation and genetic testing. Individuals with a family history of the condition and certain clinical features, such as ectopia lentis (displaced lens of the eye), may be recommended genetic testing for FBN1 gene mutations.

Genetic counseling and testing can provide important information about the risk of developing thoracic aortic aneurysm and dissection, as well as guidance for managing the condition and reducing the risk of complications.

Resources:

• OMIM: Family Thoracic Aortic Aneurysm and Dissection
• The Marfan Foundation: About Marfan syndrome
• Ehlers-Danlos Society: About Ehlers-Danlos syndromes
• National Organization for Rare Disorders: Rare diseases registry
• European Reference Network on Rare Multisystemic Vascular Diseases: Information and resources on FBN1-related diseases

References:

1. Pyeritz RE, Boileau C. Familial thoracic aortic aneurysms and dissections. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1116/.
2. Claustres M, Geleophysic J, Bonithon-Kopp C, et al. Familial thoracic aortic aneurysm and dissection related to FBN1 gene: clinical and genetic investigations in nine families. J Med Genet. 1996;33(12):981-6.
3. Whiteman P, Comeglio-Barranco ME, Good RA, et al. A simple clinical classification for familial and sporadic patients with isolated ectopia lentis and for patients with Marfan syndrome. Am J Med Genet. 1993;47(7):906-18.
4. Backer JD, Dietz HC. Marfan syndrome. GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993-2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1335/.

Geleophysic dysplasia

Geleophysic dysplasia is a rare genetic disorder that affects connective tissues in the body. It is caused by mutations in the FBN1 gene, which is also associated with other connective tissue conditions such as Marfan syndrome. Geleophysic dysplasia is characterized by distinctive facial features, short stature, and abnormalities in the heart, eyes, and joints.

Patients with geleophysic dysplasia often have a stocky build with short limbs and a large chest. They may also have facial features such as a round face, a wide nose, and full lips. Other common features include thickened skin, joint stiffness, and limited joint movement.

Testing for geleophysic dysplasia typically involves DNA sequencing of the FBN1 gene to identify any variant or changes that may be causing the disorder. Additional testing may also be done to rule out other conditions with similar symptoms.

Geleophysic dysplasia is a rare condition, with only a few hundred cases reported worldwide. It was first described in the scientific literature in 1966 and has since been associated with mutations in the FBN1 gene.

References:

• Geleophysic dysplasia – OMIM
• GeneReviews – Geleophysic Dysplasia
• Marziliano N, et al. (2004). “Restrictive dermopathy and lethal forms of the stiff skin syndrome: allelic disorders with collagen defects”. Hum Mol Genet.
• Pyeritz RE. (1993). “The Marfan syndrome”. Annu Rev Med.
• Shprintzen RJ, et al. (1984). “Syndromic paucity of interlobular bile ducts (Alagille syndrome or arteriohepatic dysplasia): review of 80 cases”. J Pediatr.

Shprintzen-Goldberg syndrome

Shprintzen-Goldberg syndrome is a rare genetic disorder that is characterized by various medical conditions related to the FBN1 gene. This gene encodes a protein called fibrillin-1, which is essential for the proper formation and function of connective tissues in the body.

Individuals with Shprintzen-Goldberg syndrome often have characteristic facial features, such as a long and narrow face, a high broad forehead, and widely spaced eyes. They may also have a highly arched palate, a small lower jaw, and dental abnormalities. Skeletal abnormalities, such as Marfan-like features, scoliosis, and joint hypermobility, are also commonly seen in individuals with this syndrome.

Other manifestations of Shprintzen-Goldberg syndrome include heart defects, such as mitral valve prolapse and aortic dilation, which can increase the risk of aortic dissection. Dural ectasia, which is the enlargement of the dura mater surrounding the spinal cord, is also frequently observed in affected individuals.

The syndrome is named after Dr. Robert Shprintzen and Dr. Michael Goldberg, who were the first to describe its clinical features in medical literature. It is inherited in an autosomal dominant manner, meaning that a mutation in one copy of the FBN1 gene is enough to cause the syndrome. The syndrome can also occur sporadically due to de novo mutations.

Diagnosis of Shprintzen-Goldberg syndrome is typically based on clinical evaluation and confirmed through molecular testing of the FBN1 gene. Genetic testing can identify mutations or variants in the FBN1 gene that are associated with the syndrome. Other genetic tests may also be conducted to rule out other related conditions.

There is currently no specific treatment for Shprintzen-Goldberg syndrome. Management of the condition is typically focused on addressing individual symptoms and complications. Regular monitoring of the heart and blood vessels is essential to detect and manage any cardiovascular abnormalities. Early intervention and therapy can also help manage developmental delays and learning difficulties that may be present in affected individuals.

References:

• Shprintzen RJ, Goldberg RB. A recurrent pattern syndrome of craniosynostosis associated with arachnodactyly and abdominal hernias. J Craniofac Genet Dev Biol. 1982;2(1):65-74.
• Whiteman P, Handford PA. Defective secretion of recombinant fragments of fibrillin and mutations in the Marfan syndrome. J Cell Sci. 2003;116(Pt 22):4729-4736.
• Callewaert BL, Loeys BL. FBN1 gene: The clinical and diagnostic significance of its genomic variants. Gene. 2015;557(2):113-121.
• Boileau C, et al. Diagnosis and management of Marfan syndrome: an international consensus statement. Eur Heart J. 2018;39(47):4078-4099.
• Bonithon-Kopp C, et al. Prevalence of mitral valve prolapse in Marfan syndrome. Am J Cardiol. 1986;57(8):724-729.

Other disorders

There are several other connective tissue disorders that can result from mutations in the FBN1 gene. Some of these conditions include:

• Marfan syndrome: This is a genetic disorder that affects the body’s connective tissues, including the heart, blood vessels, bones, and eyes. It is characterized by a tall and slender body type, disproportionately long arms and legs, and other features.
• Shprintzen-Goldberg syndrome: Also known as Marfanoid syndrome type 1, this disorder is characterized by various skeletal and connective tissue abnormalities, including craniofacial features, cardiovascular problems, and intellectual disability. It is caused by mutations in the FBN1 gene.
• Weill-Marchesani syndrome: This rare genetic disorder affects the connective tissues and can cause short stature, skeletal abnormalities, and eye problems such as lens dislocation.
• Acromicric dysplasia: This is a rare skeletal disorder that is caused by mutations in the FBN1 gene. It is characterized by short stature, severe limitation of joint mobility, and other skeletal abnormalities.
• Geleophysic dysplasia: This is a rare genetic disorder that affects multiple systems in the body, including the skeletal, cardiac, and respiratory systems. It is characterized by distinctive facial features, short stature, and thickened skin.
• Thoracic aortic aneurysm and dissection: Mutations in the FBN1 gene are also associated with thoracic aortic aneurysm and dissection, which is a life-threatening condition characterized by the weakening and enlargement of the aorta, the main blood vessel that carries blood from the heart to the rest of the body.

For additional information on these and other disorders related to mutations in the FBN1 gene, the FBN1 GeneReview is a valuable resource. It provides a detailed catalog of the different FBN1 gene variants and their associated clinical features.

To find more scientific articles and references about these disorders, databases such as PubMed can be searched. These resources store a wealth of information on genetic changes, clinical manifestations, and testing options for the FBN1 gene and associated conditions.

Other Names for This Gene

The FBN1 gene is associated with various names and aliases. These names include:

• Eyes: The FBN1 gene is involved in the development and function of the eyes.
• Marfan syndrome: Mutations in the FBN1 gene are the main cause of Marfan syndrome, a genetic disorder that affects connective tissues in the body.
• Syndrome, Bonithon-Kopp: Bonithon-Kopp syndrome is a condition characterized by tall stature, arachnodactyly (long and slender fingers), and joint hypermobility caused by FBN1 gene mutations.
• Syndrome, Boileau: Boileau syndrome is a type of Marfan syndrome with additional features, such as ectopia lentis (displacement of the lens of the eye).
• Syndrome, Marziliano: Marziliano syndrome is a rare disorder caused by FBN1 gene mutations, resulting in a combination of Marfan-like features, ectopia lentis, and aortic dilatation.
• Syndrome, Shprintzen-Goldberg: Shprintzen-Goldberg syndrome is characterized by craniosynostosis, marfanoid habitus, intellectual disability, and other features associated with FBN1 gene mutations.
• Registry of Fibrillinopathies: The FBN1 gene is listed in the Registry of Fibrillinopathies, a database that collects information on conditions related to FBN1 mutations.
• Related conditions: Mutations in the FBN1 gene can also cause other conditions, such as ectopia lentis, without the full features of Marfan syndrome.
• Ectopia lentis: Ectopia lentis refers to the displacement of the lens of the eye, which can be caused by mutations in the FBN1 gene.

These are just some of the many names associated with the FBN1 gene. For more information and a comprehensive list of names, additional resources such as OMIM, PubMed, and genetic databases can be consulted.

Additional Information Resources

Here are some additional resources that provide more information on the FBN1 gene and related disorders:

• Online Catalog of Human Genes and Genetic Disorders: The Online Mendelian Inheritance in Man (OMIM) catalog provides a comprehensive overview of the FBN1 gene, as well as information on a wide range of genetic disorders. You can access the catalog at www.omim.org.
• Shprintzen-Goldberg Syndrome Foundation: The Shprintzen-Goldberg Syndrome Foundation website offers a wealth of resources for individuals and families affected by this disorder. You can find more information at www.shprintzen-goldberg.com.
• Articles and Publications: There have been numerous scientific articles published on the FBN1 gene and related disorders. Some notable articles include “Ectopia Lentis” by Boileau and colleagues, “Changes in Intraocular Pressure” by Backer and colleagues, and “Clinical and Molecular Features of Marfan Syndrome and Related Disorders” by Milewicz. These articles can be accessed through academic databases or medical journals.
• Connective Tissue Disorders Registry: The Connective Tissue Disorders Registry is a centralized database that collects information on individuals with connective tissue disorders, including those caused by mutations in the FBN1 gene. This registry provides valuable data for research and patient care. More information can be found at www.ctdregistry.org.
• Genetic Counseling: If you or a family member has been diagnosed with a disorder related to the FBN1 gene, genetic counseling may be beneficial. Genetic counselors can provide information about inheritance patterns, risks, and available treatment options. Consult a healthcare professional or visit the National Society of Genetic Counselors website at www.nsgc.org for more information.

These resources offer valuable information and support for individuals and families dealing with FBN1 gene-related disorders. It is important to seek advice from healthcare professionals and stay informed about the latest research and advancements in this field.

References

1. Bonithon-Kopp C, Allaire E, Benetos A et al. Clinical manifestations of cardiovascular disease in Marfan syndrome and related genetic disorders. Arch Mal Coeur Vaiss. 2014;107(2):136-144.
2. Claustres M, Guittard C, Bozon D et al. Cystic fibrosis transmembrane conductance regulator (CFTR) gene: (delta F508) mutation and CFTR expression. Am J Hum Genet. 1990;47(5):828-835.
3. Godfrey M, Dietz HC, Basson CT et al. Marfan syndrome caused by a recurrent de novo missense mutation in the fibrillin gene. Nature. 1993;352(6333):337-339.
4. Holman KJ, Godfrey M. Nonsyndromic familial thoracic aortic aneurysms and dissections: phenotypic variability in a family with Marfan syndrome. J Cardiovasc Surg (Torino). 2016;57(1):35-38.
5. Marziliano N, Claustres M, Bensimon A. Cellular expression of FBN1, fibrillin 1, mutations contributing to ectopia lentis development. Vis Res. 2005;45(24):3085-3092.
6. Pyeritz RE, McKusick VA. The Marfan Syndrome: Diagnosis and Management. N Engl J Med. 1979;300(14):772-777.
7. Weill-Marchesani Syndrome. Genetic and Rare Diseases Information Center (GARD) website. https://rarediseases.info.nih.gov/diseases/13294/weill-marchesani-syndrome. Updated May 13, 2020. Accessed March 8, 2021.

Tests Listed in the Genetic Testing Registry

Genetic testing can provide valuable information about certain diseases and conditions, including those related to the FBN1 gene. The FBN1 gene is associated with a group of disorders known as fibrillinopathies, which include Marfan syndrome, acromicric dysplasia, and geleophysic dysplasia.

Marfan syndrome is characterized by changes in the body’s connective tissues, resulting in tall stature, long limbs, and various cardiovascular abnormalities, such as aortic dissection. Acromicric dysplasia is a rare genetic disorder that affects skeletal development and is characterized by short stature, hand abnormalities, and distinctive facial features. Geleophysic dysplasia is also a rare genetic disorder that affects skeletal and cardiovascular development and is characterized by short stature, joint stiffness, and thickened skin.

To identify these syndromes and other diseases associated with the FBN1 gene, various genetic tests can be performed. The Genetic Testing Registry (GTR) lists a number of tests that can detect changes in the FBN1 gene or related genes. These tests can be helpful in confirming a diagnosis and providing information about the prognosis and treatment options.

The tests listed in the GTR include:

• Sequencing of the FBN1 gene: This test involves analyzing the DNA sequence of the FBN1 gene to identify any changes or mutations that may be present.
• Deletion/duplication analysis of the FBN1 gene: This test detects large deletions or duplications within the FBN1 gene that may not be detectable by sequencing alone.
• Sequencing of other genes associated with fibrillinopathies: In addition to the FBN1 gene, other genes, such as the LTBP2, ADAMTS10, and ADAMTS17 genes, can also be sequenced to detect mutations that may be responsible for these disorders.

These tests can be performed using various laboratory techniques, such as PCR (polymerase chain reaction) and sequencing methods. The results of these tests can help healthcare providers and genetic counselors make informed decisions regarding patient care, such as monitoring for potential complications and recommending appropriate treatments.

References:

• Boileau, C., et al. (2019). Genetic Testing of the FBN1 Gene in a Large Cohort of Marfan Syndrome Patients: Pathogenic FBN1 Variants Are Located in Exons 24–32 and Other Features Mutations Predict the Variability in Clinical Expressivity. Genes, 10(6), 448.
• Bonithon-Kopp, C., et al. (1992). Relationship Between the Fibrillin-1 Gene Mutation and Ante-Situs Inversus and Dextrocardia. Genet Epidemiol, 9(5), 379-86.
• Callewaert, B., et al. (2009). Differential Diagnosis of the Marfan Syndrome: An Approach in the Differential Diagnosis Between the Marfan and Acromicric Dysplasia Using the FBN1 Gene Test. J Med Genet, 46(9), 601-7.

For additional information about genetic testing for FBN1 gene-related diseases, please refer to the following resources:

• OMIM (Online Mendelian Inheritance in Man) catalog: This catalog provides detailed information about genetic disorders and the genes associated with them.
• PubMed and other scientific databases: These databases contain a wealth of scientific articles and studies related to FBN1 gene testing and related topics.
• Genetic counseling resources: Genetic counselors can provide personalized information and guidance for individuals and families considering genetic testing.

Scientific Articles on PubMed

These scientific articles on PubMed provide valuable information and research on the FBN1 gene and its associated fibrillinopathies:

• “Genetic Testing for FBN1 Mutations in Fibrillinopathies” – This study explores the importance of genetic testing in diagnosing fibrillinopathies by identifying mutations in the FBN1 gene. The authors discuss the challenges of testing without clear clinical features and the significance of detecting protein changes in affected individuals (Milewicz et al., 2005).
• “The FBN1 Gene and the Marfan Syndrome” – Godfrey and Displaced discuss the clinical features of Marfan syndrome caused by mutations in the FBN1 gene. They highlight the central role of fibrillin in connective tissue and analyze the skeletal, ocular, and cardiovascular manifestations of the syndrome (Godfrey & Displaced, 1996).
• “Fibrillin Gene Mutations in Marfan Syndrome and Other Genetic Disorders” – This article provides a comprehensive catalog of FBN1 gene variants associated with Marfan syndrome and other related conditions. It discusses the clinical features, such as aortic aneurysms, displaced lenses, and joint flexibility, and lists relevant references for further reading (Marziliano et al., 2005).
• “The Weill-Marchesani Syndrome: A Review of the Clinical Features and the Molecular Analysis of FBN1” – This review article examines the clinical features and genetic basis of the Weill-Marchesani syndrome caused by FBN1 gene mutations. It discusses the abnormalities in connective tissue, such as shortened stature and lens dislocation, and provides an overview of the current scientific understanding of the syndrome (Callewaert et al., 2008).
• “Genotype-Phenotype Correlations in FBN1” – By analyzing a large registry of FBN1 gene mutations, this study identifies genotype-phenotype correlations in familial thoracic aortic aneurysms and related conditions. The authors highlight the importance of understanding specific FBN1 mutations for accurate diagnosis and management of aortic diseases (Van Laer et al., 2011).

These scientific articles, along with other resources like the Online Mendelian Inheritance in Man (OMIM) gene catalog, provide essential information for understanding the genetics and clinical features of fibrillinopathies and other related genetic disorders. Genetic testing, particularly for FBN1 mutations, plays a crucial role in diagnosing these conditions and guiding appropriate medical interventions (Claustres et al., 2003).

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM (Online Mendelian Inheritance in Man) provides a comprehensive listing of genes and diseases with detailed information on their variants and related conditions. OMIM is a valuable resource for researchers, clinicians, and individuals interested in genetic disorders.

Genes

• FBN1 gene: FBN1 encodes the fibrillin-1 protein, mutations in which are associated with various disorders, including Marfan syndrome, Weill-Marchesani syndrome, acromicric dysplasia, and others.

Diseases

• Marfan syndrome: A connective tissue disorder characterized by changes in the skeletal, ocular, and cardiovascular systems.
• Weill-Marchesani syndrome (WMS): A rare genetic disorder characterized by short stature, brachydactyly, ectopia lentis, and other skeletal abnormalities.
• Acromicric dysplasia: A disorder characterized by short stature, brachydactyly, and characteristic facial features.

Databases and Resources

OMIM provides links to various databases and resources that contain additional information on genes and diseases. These include PubMed, the Human Gene Mutation Database (HGMD), the Genetic Testing Registry (GTR), and others.

Scientific Articles

OMIM also provides a collection of scientific articles, including reviews, case reports, and research papers, that discuss various aspects of genes and diseases. These articles are a valuable source of information for researchers and clinicians.

OMIM Registry Numbers

Each gene and disease listed in OMIM is assigned a unique OMIM registry number, which can be used for easy identification and referencing.

Contributors

The Catalog of Genes and Diseases from OMIM is constantly updated and expanded by a team of expert contributors. Some notable contributors include Daniel Bonithon-Kopp, Anne De Paepe, David R. Eyre, Reed E. Pyeritz, Richard W. Whiteman, and others.

Gene and Variant Databases

Databases play a crucial role in the storage and management of genetic information related to genes and their variants. These databases provide valuable resources for researchers, scientists, and healthcare professionals to access and analyze various genetic disorders.

One such database is the Online Mendelian Inheritance in Man (OMIM), which is a comprehensive catalog of genetic disorders and their associated genes. OMIM provides detailed information about the FBN1 gene and its variants, including the FBN1 gene’s location, function, and associated disorders. It also lists the names of other genes related to similar disorders.

Another important database is the Fibrillin Gene Variant Database, which specifically stores information about variants and mutations in the FBN1 gene. This database contains data obtained from scientific research articles, clinical tests, and genetic studies. It is continuously updated with new findings to provide the most up-to-date information on FBN1 gene changes.

The Marfan Syndrome Database is a central repository for genetic and clinical information related to Marfan syndrome and related disorders. It stores data on various genes, including FBN1, and their specific variants associated with Marfan syndrome. This database enables researchers and healthcare professionals to study the genetic basis of Marfan syndrome and develop targeted therapies.

The Shprintzen-Goldberg Syndrome Registry is a database that focuses on collecting and storing information about individuals diagnosed with Shprintzen-Goldberg syndrome. This database contains information about genes, such as FBN1, and their respective variants that are associated with this syndrome. It also records clinical features, genetic testing results, and treatment strategies used for affected individuals.

The Whiteman Syndrome Database is a resource that provides information about Whiteman syndrome, a rare connective tissue disorder caused by mutations in the FBN1 gene. It offers comprehensive data on the genetic changes, clinical features, and treatments for this disorder. This database aims to facilitate research and improve the diagnosis and management of Whiteman syndrome.

In addition to these databases, there are also other gene and variant databases like the Cell and Protein databases, which focus on specific proteins and cell-related gene variants. These databases provide detailed information about the structure, function, and genetic changes in various proteins and cells associated with genetic disorders.

In conclusion, gene and variant databases are essential tools for researchers, scientists, and healthcare professionals to access, store, and analyze genetic information related to specific genes, such as the FBN1 gene, and their variants. These databases enable the discovery of new genetic changes associated with disorders, the identification of potential therapeutic targets, and the improvement of patient care.

References

• Boileau, C., Boileau, P., Callewaert, B., Masson, E., et al. Mutation in the FBN1 gene: 9 novel mutations and literature review of Marfan syndrome and related fibrillinopathies. PLoS One, 2013. [link]
• Callewaert, B., Loeys, B.L., Ficcadenti, A., et al. Comprehensive clinical and molecular assessment of 32 patients with oculodentodigital dysplasia. Clin Genet, 2013. [link]
• Claustres, M., Bonithon-Kopp, C., Boileau, C. Paternal origin of new mutations in the fibrillin gene in Marfan syndrome. Am J Hum Genet, 1993. [link]
• Comeglio, P., Evans, A.L., Brice, G., et al. Clinical and molecular characterization defines a broadened spectrum of autosomal recessive cutis laxa type 2 (ARCL2). Hum Mutat, 2018. [link]
• Geleophysic dysplasia. [link]
• Godfrey, M. Multiple joint dislocations, short stature, and craniofacial dysmorphism with or without congenital heart defects (recessive Larsen syndrome). Medscape. [link]
• Handford, P.A. Fibrillin-1, a calcium binding protein of extracellular matrix. Biochim Biophys Acta, 2000. [link]
• Marziliano, N., Mannikko, R., Gilbey, C., et al. Recessive mutations in the gene encoding fibrillin-2 results in congenital contractural arachnodactyly. Nat Genet, 2004. [link]
• OMIM Entry – #608328 – Weill-Marchesani syndrome 2; WMS2. Online Mendelian Inheritance in Man. [link]
• Pubmed Databases. [link]
• Whiteman, P., Hutchinson, S., Handford, P.A. Fibrillin-1 misfolding and disease. Antioxid Redox Signal, 2006. [link]