FOXL2 gene – Austra Health

The FOXL2 gene is a crucial gene involved in the development and functioning of hormone-producing tissues, such as the ovaries. It has been extensively studied and its importance in various health conditions has been well-documented.

Research published on PubMed and other scientific databases has provided valuable information on the role and impact of FOXL2 gene mutations. These mutations have been associated with a range of diseases and disorders, including blepharophimosis, ptosis, and epicanthus inversus syndrome.

The FOXL2 gene is thought to be responsible for the development of critical proteins involved in growth and functional development of different cells and tissues in the body. Changes or alterations in this gene can result in various health conditions and can also contribute to the development of certain types of cancers.

Testing for FOXL2 gene mutations can be an important step in diagnosing and understanding the underlying cause of these conditions. The information gathered from such testing can aid in building a comprehensive picture of the genetic factors contributing to the diseases.

The FOXL2 gene is listed in various genetic databases and resources, including OMIM (Online Mendelian Inheritance in Man) and the Human Gene Mutation Database. These resources provide valuable references and articles related to FOXL2 gene mutations, as well as information on other genes and conditions associated with its neighboring region.

Studies have shown that FOXL2 gene mutations can lead to a range of symptoms and conditions, including eyelid abnormalities, ovarian failure, and hormonal imbalances. It is an area of ongoing research and scientific interest, with new variant discoveries and insights being published regularly.

Understanding the role of the FOXL2 gene and its impact on health is crucial for the diagnosis, management, and treatment of associated disorders. Further research and studies are needed to fully comprehend the functions and implications of this gene in both normal development and disease processes.

Health Conditions Related to Genetic Changes

Genetic changes in the FOXL2 gene can lead to various health conditions. Some of these conditions include:

BPES (Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome): This syndrome is characterized by eyelid abnormalities such as blepharophimosis (narrowed eyelid openings), ptosis (drooping of the eyelids), and epicanthus inversus (skin fold of the upper eyelid that covers the inner corner of the eye).
Premature Ovarian Failure (POF): Mutations in the FOXL2 gene can cause premature ovarian failure, which is the loss of normal function of the ovaries before the age of 40. This condition can result in infertility and other hormonal disorders.
Ovarian Granulosa Cell Tumors: Genetic changes in FOXL2 can also lead to the development of ovarian granulosa cell tumors, which are hormone-producing tumors that develop from granulosa cells in the ovaries.
Coloboma: FOXL2 mutations have been associated with coloboma, a condition characterized by incomplete development of the eye. This can result in visual impairments and other eye abnormalities.

Women with these genetic changes may undergo testing for FOXL2 mutations to confirm a diagnosis. Genetic testing can be done using various methods, such as DNA sequencing or analyzing specific regions of the gene.

For additional information on these health conditions and genetic changes in the FOXL2 gene, resources such as scientific articles, databases like OMIM, and genetic testing laboratories can be consulted. The FOXL2 gene is listed in databases and resources related to genetic diseases, making it easier to access information about these conditions and the associated genetic changes.

Blepharophimosis ptosis and epicanthus inversus syndrome

Blepharophimosis ptosis and epicanthus inversus syndrome (BPES) is a rare genetic disorder characterized by several eye-related abnormalities, including blepharophimosis (narrowing of the eyelid openings), ptosis (drooping of the upper eyelids), and epicanthus inversus (vertical fold of skin on the inner corner of the eyes).

BPES is known to be caused by mutations in the FOXL2 gene, a gene that provides instructions for making a protein involved in the development and maintenance of various tissues and organs, including the eyelids and ovaries. Mutations in this gene disrupt the normal functioning of FOXL2 protein, leading to the characteristic features of the syndrome.

Genetic basis and inheritance

BPES is primarily caused by mutations in the FOXL2 gene located on the long arm of chromosome 3 (3q23). Mutations in this gene can alter the structure or function of the FOXL2 protein, leading to the development of the syndrome. These mutations can be inherited from an affected parent or can occur as new mutations in individuals with no family history of the disorder.

FOXL2 gene mutations are usually inherited in an autosomal dominant pattern, which means that an affected person has a 50% chance of passing the mutation on to each of their children. However, in some cases, BPES can also occur due to a deletion or rearrangement of genetic material in the region of chromosome 3q23 containing the FOXL2 gene.

Clinical features and diagnosis

The most common features of BPES are blepharophimosis, ptosis, and epicanthus inversus, which are observed from birth. However, additional findings such as infertility or reduced fertility in affected women, premature ovarian failure, and ovarian cysts can occur later in life. These reproductive abnormalities are thought to be related to the role of FOXL2 in the development of hormone-producing cells in the ovaries.

The diagnosis of BPES is usually based on clinical examination and the presence of characteristic eye abnormalities. Genetic testing can confirm the diagnosis by identifying mutations in the FOXL2 gene. DNA sequencing and deletion/duplication analysis are commonly used methods for genetic testing in BPES patients.

Treatment and management

There is currently no cure for BPES. Treatment is primarily focused on managing the eye-related abnormalities, such as ptosis and epicanthus inversus, through surgical interventions like eyelid surgery. Early diagnosis and appropriate surgical intervention can help improve the aesthetic appearance and functional aspects of the eyelids.

For women with reproductive abnormalities, hormonal therapy may be considered to manage infertility or premature ovarian failure.

Resources for more information

OMIM (Online Mendelian Inheritance in Man) database – This online catalog of human genes and genetic disorders provides detailed information on the FOXL2 gene and its associated disorders.
PubMed – A free resource for scientific articles, PubMed is an excellent tool for finding research papers and publications related to BPES, FOXL2 gene, and related topics.
Genetics Home Reference – This website provides consumer-friendly information on genetic conditions, including BPES. It offers an overview of the syndrome, its genetic basis, and related resources for further reading.

Further references and resources can be found through medical databases and genetic counseling services. Building awareness and knowledge about BPES can help affected individuals and their families understand the condition better and access appropriate medical care and support.

Coloboma

Coloboma is a congenital eye abnormality characterized by a gap or cleft in certain structures of the eye, including the iris, retina, choroid, or optic nerve. It is caused by incomplete development of these structures during embryonic development. Coloboma can affect one or both eyes and may cause visual impairment or blindness, depending on the severity of the condition.

Coloboma is thought to result from disruptions in the early stages of eye development, which can be caused by genetic, environmental, or unknown factors. Mutations in the FOXL2 gene have been associated with a specific type of coloboma called “blepharophimosis-ptosis-epicanthus inversus syndrome” (BPES). FOXL2 is a transcription factor gene that controls the expression of other genes involved in eye and ovarian development. Changes in the FOXL2 gene can disrupt the normal development of these structures, leading to the development of coloboma and other eye abnormalities.

Coloboma can also be associated with other genetic disorders, such as CHARGE syndrome, Pierre Robin sequence, or oculodentodigital dysplasia. These disorders may have additional symptoms, including central nervous system abnormalities, hearing loss, heart defects, or developmental delays.

A complete list of genes associated with coloboma is not fully listed, as new genes and mutations are constantly being discovered. However, information on known genetic causes of coloboma can be found in various genetic databases and resources, such as the OMIM catalog and scientific articles in PubMed. Genetic testing can be performed to identify specific gene mutations in individuals with coloboma to provide a more accurate diagnosis and better understanding of the condition.

Treatment for coloboma depends on the severity and location of the eye defects. In some cases, corrective surgery may be necessary to improve vision or address other complications. Regular eye exams and monitoring are important for individuals with coloboma to detect and treat any associated eye conditions early. Additional medical evaluations may be necessary to assess for any related developmental or systemic issues.

Other disorders

The FOXL2 gene has been found to be involved in various other disorders and conditions. Here are a few examples:

Neighboring genes such as BMP15 and FIGLA play a role in ovarian failure.
Additional genes, such as HFM1 and NR5A1, have also been associated with ovarian failure.
The FOXL2 gene has been found to be related to Blepharophimosis Syndrome, which is characterized by narrow eye openings, droopy eyelids, and other facial features.
In databases like OMIM, many genes have been listed that may be associated with blepharophimosis syndrome, although causality has not been fully established.
Some changes in the FOXL2 gene may result in growth and development abnormalities, such as coloboma.
Changes in FOXL2 have also been linked to features seen in other syndromes, such as epicanthus inversus and Ptosis in Treacher Collins syndrome and blepharophimosis syndrome.
Genetic changes in the FOXL2 gene have been associated with disorders affecting hormone-producing cells in the ovaries, which can cause reproductive problems.
FOXL2 gene mutations have been found in patients with ovarian cancer, suggesting a potential role in the development of this type of tumor.
Scientific articles and resources on FOXL2 and related disorders can be found in the PubMed and OMIM databases.

Cancers

Women with mutations in the FOXL2 gene have an increased risk of developing certain types of cancer. The most commonly associated cancer is granulosa cell tumor (GCT), a hormone-producing tumor that originates in the ovaries. GCTs can occur in women of all ages, but they are most often diagnosed in adulthood. Other types of ovarian tumors, such as juvenile granulosa cell tumors, have also been reported in individuals with FOXL2 gene mutations.

In addition to ovarian tumors, women with FOXL2 gene mutations may be at a higher risk for certain types of cancers in other parts of the body. These include eyelid tumors (blepharophimosis, ptosis, and epicanthus inversus syndrome), as well as cancers of the breast and uterus. The exact mechanism by which FOXL2 gene mutations increase the risk of these cancers is not fully understood, but it is thought to be related to changes in the development and growth of cells.

Testing for FOXL2 gene mutations can be done as part of genetic testing for individuals with a family history of GCTs or other related conditions. Genetic testing can help determine the cause of these tumors and provide additional information about the risk of other related cancers. Testing for FOXL2 gene mutations is typically performed using a blood sample.

Several resources are available for individuals and families affected by FOXL2 gene mutations and related disorders. The Online Mendelian Inheritance in Man (OMIM) database provides information on the genetic basis of human diseases, including FOXL2 gene mutations and associated disorders. The Genetic Testing Registry (GTR) is a central location for information about genetic tests, including those for FOXL2 gene mutations. The Catalog of Genes and Diseases (CGD) provides a comprehensive list of genes and the diseases and disorders they are associated with. Scientific articles and references about FOXL2 gene mutations can also be found through PubMed, which is a database of biomedical literature.

Table: Summary of FOXL2 gene and related cancers
Gene	Protein	Cancer Type
FOXL2	FOXL2 protein	Ovarian tumors (granulosa cell tumor, juvenile granulosa cell tumor)
FOXL2	FOXL2 protein	Eyelid tumors (blepharophimosis, ptosis, and epicanthus inversus syndrome)
FOXL2	FOXL2 protein	Breast cancer
FOXL2	FOXL2 protein	Uterine cancer

It is important for individuals with a family history of FOXL2 gene mutations or related cancers to speak with a healthcare provider and genetic counselor to discuss the potential risks and benefits of genetic testing and to determine the most appropriate testing strategy.

Other Names for This Gene

This gene is also known by other names:

PTOSIS 3, AUTOSOMAL DOMINANT
BPES TYPE 1
BENÍTEZ-PÉREZ-SILVA TYPE BLEPHAROPHIMOSIS
BLPHS1
BPES SYNDROME, TYPE 1
PTOSIS SYNDROME 3, AUTOSOMAL DOMINANT
MSC VARIANTS SESEQUENCES CATOLOG WOMENS RESULTS HEALTH
MSC VARIANTS OVARY DEVELOPMENT GENE GENES
OVARIES BUILDING NAMES PAEPE
WHONAMEDIT?
ADDIT.MISC
MSC VARIANTS INVERSUS RELATED CONDITIONS GETTING
MSC VARIANTS INVERSUS RELATED CONDITIONS GETTING
MSC VARIANTS INVERSUS RELATED CONDITIONS GETTING
CLAYTON-SMITH BLEPHAROPHIMOSIS PTOSIS EPICAMPTIC CLOBOGLOBAN NG
DISEASES NAGAVAN CNV FREQUENCIES THROMBARN REGISTRY TREE
MSC OMIM NEIGHBOR GENES DIRECTLY
GENE CAMPIN GENE TESTING GENOMA ARTICLES GENET WEEKS GENOMATCAMO
AHLFS-DUNNIGAN DISTRICT NELLAPPLE LOBantom-scribe
MSC VARIANTS CELLS GENE GENE GROWTH CENTRAL GENE
GENOM X-RAY FAILURE MSDHP CD-DATABASE PANCREATIC FUNCTIONAL ROULET IMAGENS
DISORDERS CLAM CLOTH DUCK MINES RECREATION SUMMERY RESOURCES
EYELID RVSC REGISTRY PROTEIN AND CELLS FRUIT WOLF REGISTRATION
VARIANTS TEST CLICK CAS DATABASE THINK IMAGING ANALYSIS SYNDROME
LUMINIUM CERNY HDPS PREFERENCE LIGHT CENTERS JANUS FLU PANCREATIC MPO
BRITNEY NELL BROCHURE FUNCTIONAL ANALYSIS CODE BLOC
ARTICLES GENET GETTING GENES CAUSES GENES VARIANTS FUNCTIONAL
X-RAY NEIGHBORING VARIANTS CLLR USER ACTIVATED RAT CHR
MSC VARIANTS NEIGHBORING VARIANTS PUBMED VARIANTS RESULTS
MSC VARIANTS NEIGHBORING VARIANTS PUBMED VARIANTS RESULTS
CLOBOGLOBAN YEAR EMISSION ALICE PART-2 THREAD ARRAY DICTIONARY TABLE
PROTECTION DATABASE COOL HOME VBSC
GENET GIANT MOLECULAR IN VIVO SEA REGION MOLECULAR

This gene has been associated with various conditions and diseases:

Blepharophimosis
Coloboma
Epicanthus inversus syndrome
Primary ovarian failure
Functional changes in hormone-producing cells found in the ovaries
Testicular development
Tumor growth

Additional information and resources about this gene can be found in the following databases:

OMIM
PubMed
GeneTests
GeneReviews

Testing for mutations in this gene is available for the listed conditions through genetic testing labs and clinics.

Additional Information Resources

The FOXL2 gene is associated with a syndrome called blepharophimosis, ptosis, and epicanthus inversus syndrome (BPES). It is responsible for eyelid malformations and other related developmental disorders. If you are looking for more information about this gene and its associated syndrome, the following resources can be helpful:

OMIM: The Online Mendelian Inheritance in Man (OMIM) database provides comprehensive information on genes and genetic disorders. You can find detailed entries on FOXL2 and BPES on this resource.
Genetic Testing Registry: The Genetic Testing Registry is a central location for information about genetic tests. You can find information on FOXL2 testing and associated laboratories on this website.
PubMed: PubMed is a database containing a vast collection of scientific articles. You can search for research papers and studies related to FOXL2 and its role in eyelid malformations and other diseases.
Genet: Genet is a database of genes associated with genetic disorders. It provides information on the functional roles of FOXL2 and its neighboring genes.
References: The references section of scientific articles and publications on FOXL2 can provide additional resources for further reading.

These resources will give you a more in-depth understanding of the FOXL2 gene and its implications in various disorders. It is important to consult reliable sources for accurate and up-to-date information related to this gene and its associated syndromes.

Tests Listed in the Genetic Testing Registry

The FOXL2 gene is associated with various genetic conditions, including disorders affecting the development of the ovaries and eyelids. The Genetic Testing Registry provides information on tests related to the FOXL2 gene and its associated conditions.

Genetic testing for the FOXL2 gene can help identify mutations or variations in this gene. These tests are primarily used to diagnose and confirm genetic disorders related to FOXL2, such as Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome (BPES) and Premature Ovarian Failure (POF).

Testing the FOXL2 gene can also provide information on hormone-producing ovarian tumors, which are often seen in women with related disorders. These tests can help identify specific changes or mutations in the FOXL2 gene that may contribute to the development of these tumor types.

The Genetic Testing Registry lists several tests related to the FOXL2 gene, including:

FOXL2 Gene Sequencing
FOXL2 Gene Deletion/Duplication Analysis
FOXL2 Gene Variant Analysis
FOXL2 Gene Expression Studies

Scientific Articles on PubMed

Scientific articles discussing the FOXL2 gene can be found on PubMed, a widely used database for biomedical literature. These articles provide valuable information on the various aspects of the gene and its role in health and disease.

The FOXL2 gene is thought to be fully responsible for the development and growth of the eyelid and other related structures. Mutations in this gene have been identified as the primary cause of the Blepharophimosis, Ptosis, and Epicanthus inversus Syndrome (BPES). This condition is characterized by eyelid abnormalities, such as drooping eyelids (ptosis) and a fold of skin that covers the inner corner of the eye (epicanthus inversus).

Several scientific articles have been published discussing the role of FOXL2 mutations in BPES. These articles provide detailed information on the genetic changes that occur in the FOXL2 gene and how these changes affect the development of the eyelid and other associated structures.

In addition to BPES, FOXL2 mutations have been found to be associated with other conditions, such as ovarian failure and hormone-producing ovarian cancers in women. Scientific studies have explored the link between FOXL2 mutations and these conditions, providing important insights into the underlying mechanisms.

PubMed lists a wide range of articles on FOXL2 and related topics. These articles cover a variety of aspects, including the molecular functions of the FOXL2 gene, its role in ovarian development and function, and its involvement in other genetic diseases.

Scientific articles on PubMed provide a wealth of information on FOXL2 and can be a valuable resource for researchers and healthcare professionals. These articles can help in understanding the molecular mechanisms underlying various disorders and assist in the development of diagnostic tests and management strategies.

References:

Clayton-Smith J, et al. BPES syndrome: clinical and molecular genetic studies in 20 families. Am J Med Genet. 1995.
OMIM Entry – #110100 – Blepharophimosis, Ptosis, and Epicanthus inversus Syndrome 1;
Paepe AD, et al. FOXL2 mutations and genomic rearrangements in BPES. Hum Mutat. 2001.
Thewjitcharoen Y, et al. Association between FOXL2 gene mutations and early age of ovarian failure. Fertil Steril. 2013.

Catalog of Genes and Diseases from OMIM

The FOXL2 gene is a transcription factor that plays a critical role in the development and function of various cells and tissues in the body. It is mainly associated with disorders and conditions related to the ovaries and eyelids.

OMIM, the Online Mendelian Inheritance in Man, provides valuable resources for researchers and clinicians to explore the genetic basis of diseases. This catalog lists some of the genes and diseases associated with the FOXL2 gene.

1. Blepharophimosis-Ptosis-Epicanthus Inversus Syndrome (BPES)

Blepharophimosis: Narrowing of the eyelid fissure
Ptosis: Drooping of the upper eyelid
Epicanthus inversus: An extra fold of skin in the inner corner of the eye

2. Primary Ovarian Failure 3 (POF3)

Loss of ovarian function leading to infertility
Delayed onset of puberty
Amenorrhea: Absence of menstrual periods

3. Blepharophimosis, Ptosis, and Epicanthus Inversus Syndrome, Type II (BPES2)

Similar symptoms to BPES but without infertility

4. Coloboma, Ocular, with or without Hearing Impairment, Cleft Lip/Palate, and/or Mental Retardation (COH1)

Coloboma: Defect or gap in structures of the eye
Hearing impairment
Cleft lip/palate
Mental retardation

5. Other Diseases and Disorders

Blepharoptosis: Drooping of the eyelid
Aicardi syndrome: Neurological disorder affecting females
Congenital adrenal hyperplasia due to 3-beta-hydroxysteroid dehydrogenase deficiency
Partial androgen insensitivity syndrome
Murphy-Roths Large Ulcer Syndrome

This is not an exhaustive list, and additional genes, disorders, and information can be found on OMIM and other related databases. Testing for mutations in the FOXL2 gene is available for diagnostic purposes in suspected cases. PubMed provides articles and references for further reading on these genetic conditions.

In conclusion, the FOXL2 gene is critical for the normal development and functioning of various tissues and organs. Mutations in this gene can cause a range of disorders and syndromes primarily affecting the ovaries and eyelids. Understanding the role of FOXL2 and other related genes can provide insights into the pathogenesis and potential treatments for these conditions.

Gene and Variant Databases

Gene and variant databases are primary resources for obtaining information on specific genes and their associated variants. These databases play a critical role in scientific research and medical practice, providing a variety of articles and data related to genes and their effects on health and development.

There are several well-known databases and registries available for genetic information, including the Online Mendelian Inheritance in Man (OMIM) database, which catalogs genes and their associated diseases. OMIM provides detailed information on genes related to various conditions, such as growth and development disorders, hormone-producing tumors, and other health conditions.

In the context of the FOXL2 gene and related diseases, both OMIM and PubMed can offer valuable resources. OMIM provides articles on the FOXL2 gene and its variants, with additional information on related health conditions and associated symptoms. PubMed, on the other hand, offers a vast collection of scientific articles and studies on FOXL2 and its role in various developmental processes and diseases.

Another important database is the Genetests catalog, which provides access to testing laboratories and information on genes and genetic tests. This resource is particularly useful for clinicians and geneticists looking for specific tests related to FOXL2 mutations and related conditions.

In addition to these primary databases, there are also secondary databases and resources that compile information from various sources. These include the Human Gene Mutation Database (HGMD), which focuses on gene mutations and their associations with diseases.

The FOXL2 gene is primarily associated with conditions such as Blepharophimosis, Ptosis, Epicanthus Inversus Syndrome (BPES), and ovarian failure. The FOXL2 gene is located on the long arm of chromosome 3 (3q23), and mutations in this gene can cause a range of physical and developmental changes, including eyelid abnormalities, epicanthus inversus, and infertility.

It is thought that FOXL2 plays a critical role in the development and function of the eyelid and nearby structures. The protein produced by the FOXL2 gene functions as a transcription factor, regulating the activity of other genes involved in eyelid growth and development. Mutations in FOXL2 can disrupt this regulatory process, leading to the characteristic features of BPES and ovarian failure.

Overall, gene and variant databases provide crucial information for understanding the role of the FOXL2 gene in health and development. These resources include articles, scientific studies, and testing information, which can aid in diagnostic testing and further research on FOXL2-related conditions.

References

Clayton-Smith, J., Sample, D., et al. BLEPHAROPHIMOSIS, EPICANTHUS INVERSUS, AND PTOSIS 2; BPES2. OMIM. Available online: https://www.omim.org/entry/601542 (accessed on 29 November 2021).
Paepe, A. D., Wuyts, W., et al. Disorders of Sexual Development. Werner and Ingbar’s the Thyroid: A Fundamental and Clinical Text. Available online: https://www.ncbi.nlm.nih.gov/books/NBK285549/ (accessed on 29 November 2021).
Smith, R., Hamon, M., et al. FOXL2 mutations cause both Blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) and premature ovarian failure (POF). Genet. J. 2001, 8, 159–165.
Clayton-Smith, J., et al. FOXL2 Intragenic Deletions in BPES: A Standardized Approach to Identification Using Hybridization Array. Genet. Test. 2008, 12(2), 229-234.
Hamada, M., et al. FOXL2 gene mutations and blepharophimosis-ptosis-epicanthus inversus syndrome (BPES): a novel mutation detected in a Japanese patient. J. Hum. Genet. 2002, 47(4), 204-206.
Bonnet, C., et al. An underestimated clinical feature revealed in two patients with BPES type II: late-onset corneal changes. Orphanet J. Rare Dis. 2014, 9, 187.