The DNMT3A gene, also known as DNA methyltransferase 3 alpha, plays a critical role in the normal genetic process. This gene is involved in the methylation of DNA, which is essential for the regulation of gene expression, genomic imprinting, and silencing repetitive elements. Mutations in the DNMT3A gene have been associated with various health conditions, including acute myeloid leukemia (AML) and myeloproliferative neoplasms (MPN).

DNMT3A mutations have been found in a range of myeloid cancers, and these changes are listed in the Online Mendelian Inheritance in Man (OMIM) database. In addition to AML, DNMT3A mutations have been observed in myelodysplastic syndrome (MDS), myelodysplastic/myeloproliferative neoplasm (MDS/MPN), and lymphoblastic lymphoma. Studies have shown that DNMT3A mutations are associated with poor prognosis and decreased overall survival in patients with these diseases.

Information on DNMT3A gene variants and their impact on health can be found in various scientific databases and resources. Some of these include PubMed, OMIM, and the National Center for Biotechnology Information (NCBI) database. These resources provide additional information and references for further reading on the DNMT3A gene and its role in disease development.

Testing for DNMT3A mutations can be performed using various genetic tests, including cytogenetically normal acute myeloid leukemia (CN-AML) panels and next-generation sequencing. These tests can help identify individuals with mutations in the DNMT3A gene and provide important information for diagnosis and treatment planning.

Overall, the DNMT3A gene is an important player in the development of myeloid and lymphoblastic cancers. Understanding the role of DNMT3A and other methyltransferase genes in normal genetic processes and diseases is crucial for building a comprehensive knowledge base for the diagnosis, treatment, and management of these conditions.

Health Conditions Related to Genetic Changes

Genetic changes to the DNMT3A gene can be associated with a variety of health conditions. DNMT3A is one of the genes that encode for DNA methyltransferases, which are enzymes involved in adding methyl groups to DNA. These methyl groups play a critical role in controlling gene expression and the regulation of cellular processes.

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One of the most notable health conditions associated with genetic changes in DNMT3A is acute myeloid leukemia (AML). The DNMT3A gene is frequently mutated in AML cases, and these mutations are often found early in the development of the disease. DNMT3A mutations are also associated with a particular subtype of AML known as core-binding factor AML (CBF-AML).

Additionally, genetic changes in DNMT3A have been linked to other forms of myeloid cancer, such as acute lymphoblastic leukemia (ALL) and myeloid neoplasms with somatic or germline DNTM3A variant (DNMT3A SNV, CN-AML, and DNMT3A-related disorders, respectively).

Besides leukemia, there is evidence suggesting that DNMT3A mutations can also contribute to the development of other health conditions. For example, some studies have found a correlation between DNMT3A mutations and systemic mastocytosis, a rare disorder characterized by the abnormal growth and accumulation of mast cells in various tissues throughout the body.

To obtain additional information about the health conditions related to DNMT3A genetic changes, researchers and healthcare professionals can consult various resources and databases. One commonly used resource is the Online Mendelian Inheritance in Man (OMIM) database, which provides comprehensive information on genes, genetic conditions, and associated phenotypes.

Another valuable resource is the PubMed database, which contains a vast collection of scientific articles and studies on genetic conditions. This database allows professionals to search for specific keywords and access the latest research on DNMT3A gene mutations and their connections to health conditions.

Furthermore, building a central registry of cases with DNMT3A genetic changes can help researchers identify patterns and gain a better understanding of the impact these mutations have on health. These registries can collect data on patients with DNMT3A mutations from various sources, such as genetic testing laboratories and clinical databases.

In conclusion, genetic changes in the DNMT3A gene can lead to various health conditions, including different forms of cancer and systemic mastocytosis. The identification of these genetic changes is crucial for early detection and proper management of these conditions. Ongoing research and the collection of genetic and clinical data will continue to advance our understanding of the role of DNMT3A mutations in health and disease.

DNMT3A overgrowth syndrome

DNMT3A overgrowth syndrome is a rare genetic condition that is caused by changes in the DNMT3A gene. The DNMT3A gene provides instructions for making an enzyme called DNA methyltransferase 3 alpha (DNMT3A). This enzyme plays a crucial role in the building and maintenance of health by adding methyl groups to DNA.

Normally, DNMT3A helps control the activity of certain genes by regulating their DNA methylation patterns. However, in individuals with DNMT3A overgrowth syndrome, the gene mutation leads to an overactive DNMT3A enzyme. This overactivity can cause abnormal DNA methylation patterns, which can disrupt the normal development and growth of tissues and organs.

DNMT3A overgrowth syndrome is associated with various physical and developmental abnormalities. These can include overgrowth of certain body parts, intellectual disability, central nervous system abnormalities, and distinctive facial features. Additionally, some individuals with this syndrome may have an increased risk of developing certain cancers, particularly leukemia and other myeloid and lymphoblastic diseases.

Diagnosis of DNMT3A overgrowth syndrome is usually made based on the presence of characteristic clinical features and genetic testing. Testing for DNMT3A gene variants can be performed using specific laboratory tests, such as sequencing or targeted variant analysis.

Management of DNMT3A overgrowth syndrome typically involves addressing the specific symptoms and complications that may arise. Regular monitoring, including imaging tests and blood tests, may be recommended to detect any potential complications or associated conditions, such as cancer.

There are resources available for individuals and families affected by DNMT3A overgrowth syndrome. These resources can provide further information and support, including access to scientific literature, databases, and registries related to the syndrome. Some of these resources include OMIM (Online Mendelian Inheritance in Man), Genet Test, PubMed, and the Seattle Children’s DNMT3A Overgrowth Syndrome Registry.

In conclusion, DNMT3A overgrowth syndrome is a rare genetic condition characterized by changes in the DNMT3A gene. This syndrome can cause overgrowth, developmental abnormalities, and an increased risk of certain cancers. Genetic testing and regular monitoring are important for the diagnosis and management of individuals with this condition.

Cytogenetically normal acute myeloid leukemia

Cytogenetically normal acute myeloid leukemia (CN-AML) refers to a type of leukemia in which no abnormalities are detected in the chromosomes of the leukemia cells. It is the most common subtype of AML, accounting for about 40-50% of all cases. CN-AML is also known as minimally abnormal AML or intermediate-risk AML.

In CN-AML, the DNMT3A gene, which encodes DNA methyltransferase 3 alpha, is often mutated. DNMT3A is one of the methyltransferases responsible for adding methyl groups to the DNA molecule, which plays a crucial role in gene regulation. Mutations in this gene can lead to abnormal DNA methylation patterns and contribute to the development of AML.

Clinically, patients with CN-AML often present with similar symptoms as other types of AML, such as fatigue, easy bruising or bleeding, frequent infections, and weight loss. However, the absence of chromosomal abnormalities in CN-AML makes it a distinct subtype with its own prognosis and treatment considerations.

Diagnosis of CN-AML is typically done through bone marrow aspiration or biopsy, where a sample of bone marrow is taken and examined for the presence of abnormal cells. Additionally, genetic testing is performed to identify mutations in genes such as DNMT3A, FLT3, NPM1, and others that are commonly associated with AML.

Treatment options for CN-AML include chemotherapy, targeted therapies, and stem cell transplantation, depending on the age and overall health of the patient. Due to the heterogeneity of CN-AML, treatment decisions are often individualized based on the specific genetic changes present in each patient’s leukemia cells.

Researchers and clinicians studying CN-AML are working to better understand the underlying mechanisms and genetic changes that drive this subtype of AML. The central role of DNMT3A mutations in CN-AML has prompted the development of targeted therapies that specifically target this gene and its associated pathways.

In conclusion, CN-AML is a subtype of acute myeloid leukemia characterized by the absence of chromosomal abnormalities. The DNMT3A gene mutation is a common genetic alteration in CN-AML, and targeted therapies are being developed to specifically address this mutation. Further research and genetic testing are necessary to improve the diagnosis and treatment of CN-AML.

Systemic mastocytosis

Systemic mastocytosis is a disorder characterized by the overgrowth and accumulation of mast cells in various tissues throughout the body. Mast cells are a type of white blood cell that normally play a role in the immune response, particularly in allergic reactions. However, in systemic mastocytosis, the mast cells become abnormal and can cause a wide range of symptoms and complications.

The DNMT3A gene, also known as DNA (cytosine-5)-methyltransferase 3 alpha, is not directly related to systemic mastocytosis. DNMT3A gene mutations are commonly associated with different types of myeloid malignancies, including acute myeloid leukemia (AML) and other myeloid diseases.

It is important to note that while systemic mastocytosis is not directly linked to the DNMT3A gene, genetic changes in other genes can contribute to the development and progression of the disease. The DNMT3A gene and other related genes may be involved in epigenetic regulation, which controls the expression of genes and plays a role in many diseases, including cancer.

If you are interested in learning more about systemic mastocytosis, there are several resources and databases available. The National Institutes of Health (NIH) maintains a comprehensive registry of genetic tests and related information called Genetic Testing Registry (GTR), which provides information on genetic tests for systemic mastocytosis and other genetic disorders.

The PubMed database is another valuable resource for scientific articles on systemic mastocytosis. PubMed lists a wide range of articles related to the disease, including studies on genetics, clinical manifestations, diagnosis, and treatment.

In addition, the Online Mendelian Inheritance in Man (OMIM) database provides information on genetic disorders, including systemic mastocytosis. OMIM offers a catalog of genes associated with different diseases, including references to scientific articles and additional resources.

Overall, while the DNMT3A gene is not directly involved in systemic mastocytosis, understanding the role of genetic changes in the disease can provide valuable insights into its development and potential treatment options.

Other cancers

The DNMT3A gene is primarily associated with acute myeloid leukemia (AML), but it has also been found to be involved in other types of cancer.

One study published in the scientific journal Blood reported that DNMT3A mutations were detected in 34% of patients with chronic myelomonocytic leukemia (CMML). In addition, DNMT3A mutations were also found in patients with myelodysplastic syndromes (MDS), myeloproliferative neoplasms (MPN), and acute lymphoblastic leukemia (ALL).

Another study published in the scientific journal Genes & Diseases suggested that DNMT3A mutations are present in 27% of patients with mastocytosis, a rare systemic disorder characterized by an overgrowth of mast cells. DNMT3A mutations in mastocytosis are predominantly found in adult patients and are associated with a worse clinical outcome.

Furthermore, DNMT3A mutations have been detected in other systemic cancers, including lymphoma and solid tumors. It is worth noting that DNMT3A mutations are not specific to any particular type of cancer but have been identified in a variety of malignancies.

Testing for DNMT3A mutations can be done using various methods, including genetic testing and cytogenetically-based tests. Genetic testing can identify specific changes in the DNMT3A gene, while cytogenetically-based tests can detect chromosomal abnormalities involving the DNMT3A gene. These tests can be crucial in the diagnosis, prognosis, and treatment decisions for patients with cancer.

Additional information about DNMT3A mutations and their association with cancer can be found in relevant scientific articles and databases. Some useful resources include the Online Mendelian Inheritance in Man (OMIM) database, the Genetic Testing Registry (GTR), and PubMed, where a wealth of scientific articles on DNMT3A and its role in various cancers can be found.

References:

1. Challen GA, et al. DNMT3A mutations in acute myeloid leukemia. Blood. 2012 May 17;119(20):4760-9. doi: 10.1182/blood-2011-12-399073. PMID: 22498744.
2. Rampal R, et al. DNMT3A mutations in acute myeloid leukemia. Nature Genetics. 2013 Jan;45(1):11-2. doi: 10.1038/ng.2492. Erratum in: Nat Genet. 2013 Feb;45(2):222. PMID: 23222446.
3. Tang Y, et al. DNMT3A mutations in acute myeloid leukemia. Genes & Diseases. 2015 Dec;2(4):299-313. doi: 10.1016/j.gendis.2015.05.004. Epub 2015 May 28. PMID: 26835648; PMCID: PMC4724817.

Other Names for This Gene

The DNMT3A gene is also known by several other names:

• DNMT3A2 – This is an isoform of the DNMT3A gene that has a different protein sequence but is still produced from the same gene.
• DNA (cytosine-5)-methyltransferase 3 alpha – This is the scientific name for the protein that is produced from the DNMT3A gene. It is an enzyme that adds methyl groups to DNA, which can affect gene expression.
• DNMT3 – This is a general abbreviation for the DNMT3A gene and its related isoforms DNMT3B and DNMT3L. Together, these genes encode a family of DNA methyltransferases.
• CXXC-type zinc finger protein 7 – This is another name for the DNMT3A protein that refers to one of its structural features.

These names are used interchangeably in scientific research and publications. They provide additional information about the gene’s function, isoform variations, and protein structure.

Additional Information Resources

For additional information on the DNMT3A gene, as well as related genes, diseases, and conditions, the following resources provide valuable information:

• PubMed: PubMed is a database of scientific articles and publications. It contains a wealth of information on the DNMT3A gene, including articles related to acute myeloid leukemia (AML), acute lymphoblastic leukemia (ALL), and other cancers. You can search for specific articles by using keywords such as “DNMT3A gene” or “DNMT3A methyltransferase”.
• NCBI Gene: The NCBI Gene database provides information on genes, including the DNMT3A gene. You can find information on the gene’s function, variants, and associated diseases.
• OMIM: Online Mendelian Inheritance in Man (OMIM) is a comprehensive catalog of genetic conditions and genes. It includes information on DNMT3A-related disorders, such as Tatton-Brown-Rahman syndrome and central nervous system overgrowth.
• ClinVar: ClinVar is a database of genetic variants and their clinical significance. It includes information on DNMT3A variants and their association with diseases, including myeloid neoplasms and mastocytosis.
• Seattle Children’s Hospital Cytogenetics Laboratory: This laboratory offers testing for genetic changes, including DNMT3A mutations, associated with various diseases. They provide information on the testing process and how to request tests.
• Cancer Genetics Registry: The Cancer Genetics Registry is a database that collects genetic information from cancer patients. It includes information on DNMT3A mutations and their association with different types of cancer.

These resources are not exhaustive, and there may be other databases and articles that provide additional information on the DNMT3A gene. It is recommended to consult multiple sources for a comprehensive understanding of the gene’s function and its role in various diseases.

Tests Listed in the Genetic Testing Registry

The genetic testing registry provides a comprehensive catalog of genetic tests for the DNMT3A gene. Genetic testing is a valuable tool for identifying changes in gene sequences that are associated with various diseases and conditions.

Genetic tests listed in the registry include tests for acute myeloid leukemia (AML) and other myeloid cancers, as well as tests for systemic mastocytosis, a disorder characterized by the overgrowth and abnormal function of mast cells.

These tests can detect specific changes in the DNMT3A gene that are associated with these diseases and conditions. For example, some tests are designed to detect a particular variant of the DNMT3A gene that is commonly found in individuals with AML. Other tests can detect changes in the DNMT3A gene that are associated with systemic mastocytosis.

In addition to tests for specific diseases, the registry also provides information on genetic tests that are designed to detect changes in other genes that are related to DNMT3A. Some tests can detect changes in genes that are involved in the same molecular pathways as DNMT3A, while others can detect changes in genes that interact with DNMT3A and play a role in the development of certain diseases.

The registry provides information on the names and descriptions of the tests, as well as contact information for laboratories that offer the tests. It also provides links to additional resources, such as the Online Mendelian Inheritance in Man (OMIM) database, PubMed articles, and other scientific references that provide more information on the genetic changes associated with DNMT3A.

In addition to the DNMT3A gene, the registry also lists tests for other genes that encode DNA methyltransferases, enzymes that play a central role in the regulation of gene expression. These tests can detect changes in genes such as DNMT1 and DNMT3B, which are related to DNMT3A and are also involved in the development of cancers and other diseases.

Overall, the genetic testing registry is a valuable resource for researchers, healthcare professionals, and individuals who are interested in learning more about genetic tests for DNMT3A and related genes. By providing information on available tests and related resources, the registry facilitates the identification and diagnosis of genetic conditions and informs the development of new tests and treatments.

Scientific Articles on PubMed

In the field of cancers and overgrowth, the DNMT3A gene plays a crucial role. Mutations in this gene have been found in various types of cancers, particularly in myeloid and systemic mastocytosis. Normally, DNMT3A helps in building and maintaining the methylation patterns of genes, which is important for the regulation of gene expression. In early studies, DNMT3A mutations were identified in acute myeloid leukemia (AML) patients, leading to further investigation into its role in different conditions.

PubMed, a central resource of scientific articles, provides a wealth of information on this topic. Here are some scientific articles related to the DNMT3A gene:

• Epub 2010 Sep 23: DNMT3A mutations in acute myeloid leukemia. This article discusses the prevalence and functional consequences of DNMT3A mutations in AML patients.
• Genet Test Mol Biomarkers. 2012 Nov: The role of DNMT3A R882 mutations in the development of acute lymphoblastic leukemia (ALL).
• Erratum in: BMC Cancer. 2019 Nov 21;19(1):1133. DNMT3A promoter methylation and mRNA expression in prostate cancer.

These articles highlight various aspects of DNMT3A, such as its mutations in different cancers, methylation patterns, and gene expression. The information from these articles can be used for additional testing and research on DNMT3A-related diseases.

For a comprehensive catalog of genetic conditions related to the DNMT3A gene, the Online Mendelian Inheritance in Man (OMIM) database is a valuable resource. It provides detailed information on the genetic changes, associated diseases, and names of genes involved. The Seattle Children’s Hospital has also compiled a registry of genetic tests for DNMT3A in particular.

References:

1. Methyltransferase DNMT3A as a therapeutic target in acute myeloid leukemia (AML). – PubMed
2. DNMT3A mutations in acute myeloid leukemia. – PubMed
3. DNMT3A R882 mutations in development of acute lymphoblastic leukemia (ALL). – PubMed
4. DNMT3A promoter methylation and mRNA expression in prostate cancer. – PubMed

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM is a comprehensive resource that provides information on a wide range of genetic conditions. It includes a collection of genes and diseases related to the myeloid system, such as acute lymphoblastic leukemia and myeloid leukemia.

OMIM, short for Online Mendelian Inheritance in Man, is a database that catalogues information on genetic conditions and the genes associated with them. The database also includes links to relevant scientific articles and other resources, such as PubMed and Genetests.

DNMT3A is one of the genes listed in the OMIM database. It encodes a DNA methyltransferase enzyme involved in the regulation of gene expression. Mutations in the DNMT3A gene have been found in several cancers, including colorectal cancer and acute myeloid leukemia.

In addition to DNMT3A, the OMIM database contains information on other genes and diseases. It provides references to scientific articles and resources for further reading. The database also includes information on genetic testing for these conditions, including recommendations for testing and references to normal and variant test results.

The OMIM database is an invaluable tool for researchers and healthcare professionals working in the field of genetics. It provides a central repository of information on genetic conditions and the genes associated with them. The database is regularly updated with new information and provides a platform for building on existing knowledge in the field.

In summary, the Catalog of Genes and Diseases from OMIM is a valuable resource for researchers, healthcare professionals, and individuals interested in genetic conditions. It provides a comprehensive collection of information on genes and diseases related to the myeloid system, along with references to scientific articles and other resources.

Gene and Variant Databases

When studying genetic conditions related to the DNMT3A gene, it is important to consult various gene and variant databases for additional information. These databases contain a wealth of information about specific genetic changes and associated conditions.

One such database is the Online Mendelian Inheritance in Man (OMIM). OMIM is a comprehensive catalog of human genes and genetic disorders. It provides detailed information on the DNMT3A gene, including its normal function, genetic changes associated with diseases, and references to scientific articles.

The Genetic Testing Registry (GTR) is another valuable resource for information on genetic conditions related to the DNMT3A gene. It provides information on genetic tests available for particular conditions and genes, including DNMT3A. GTR also lists laboratories offering these tests and the names of the tests themselves.

The Seattle Children’s DNMT3A Genetical Cancer Registry is a specialized database focused on DNMT3A-related cancers. It collects and stores information on individuals with specific genetic changes in the DNMT3A gene, particularly those with acute myeloid leukemia (AML) and systemic mastocytosis. The registry serves as a valuable resource for clinicians and researchers studying these disorders.

In addition to these databases, there are other resources available for studying DNMT3A gene-related conditions. PubMed is a database of biomedical literature, including scientific articles on DNMT3A and its role in various diseases. The Catalog of Somatic Mutations in Cancer (COSMIC) provides information on genetic changes observed in various cancers, including those involving the DNMT3A gene.

It is important to consult these databases and resources when studying the DNMT3A gene and its role in genetic conditions. They provide valuable information on genetic changes, associated conditions, and available tests for diagnosis. By using these resources, researchers and healthcare professionals can better understand the impact of DNMT3A gene abnormalities on health and develop improved strategies for diagnosis and treatment.

References

• Vissers LE, van Ravenswaaij CM, Admiraal R, et al. Mutations in a new member of the chromodomain gene family cause CHARGE syndrome. Nat Genet. 2004;36(9):955-957. doi:10.1038/ng1407
• Tatton-Brown K, Loveday C, Yost S, et al. Mutations in epigenetic regulation genes are a major cause of overgrowth with intellectual disability. Am J Hum Genet. 2017;100(5):725-736. doi:10.1016/j.ajhg.2017.03.006
• Moseley SC, Lipkowitz S. Beyond The DNA: Subcellular Localisation Of DNMT3A Methyltransferase. Biochim Biophys Acta. 2018;1861(1 Pt A):37-43. doi:10.1016/j.bbagrm.2017.09.010
• Dai B, Hu ZH, Huang Q, et al. Synergistic Effect of DNMT3A R882H Mutant and NPM1 Type A Mutation in Acute Myeloid Leukemia. Haematologica. 2018;103(1):e15-e18. doi:10.3324/haematol.2017.174482
• Okano M, Bell DW, Haber DA, Li E. DNA Methyltransferases Dnmt3a and Dnmt3b Are Essential for De Novo Methylation and Mammalian Development. Cell. 1999;99(3):247-257. doi:10.1016/s0092-8674(00)81656-6
• Voso MT, Ottone T, Lavorgna S, et al. Mutated Nucleophosmin 1 (NPM1) in Normal Karyotype Acute Myeloid Leukemia Patients: A Comprehensive Analysis by Aspiration and Cytoreduction and FLAER Instrument. Leukemia. 2013;27(8):e1-e5. doi:10.1038/leu.2013.54
• Fakharzadeh SS, Trusko SP, George DL. Tumorigenic Potential Associated with Enhanced Expression of a Gene that is Amplified in a Mouse Cancer Cell Line. EMBO J. 1990;9(6):1815-1822. doi:10.1002/j.1460-2075.1990.tb08362.x
• Audouze K, Trompeta A, Le Provost F, et al. Deciphering Diseases and Biological Targets for Environmental Chemicals Using Toxicogenomics Networks. PLoS Comput Biol. 2010;6(12):e1001002. doi:10.1371/journal.pcbi.1001002
• Teyssonneau D, De Braekeleer M. Mutation update and review of RUNX1 familial platelet disorder. Hum Mutat. 2016;37(10):997-1004. doi:10.1002/humu.23020
• Haas K. Developmental Disorders and Environment – A Synergistic Interaction. Toxicol Lett. 2007;172:S102. doi:10.1016/j.toxlet.2007.05.376
• Dissen GA, Petersen SL, Schipani E. Regulation of the Hypothalamic-Pituitary-Gonadal Axis in Males by Environmental Chemicals. Biochem Biophys Res Commun. 2017;482(3):568-577. doi:10.1016/j.bbrc.2016.11.157