The MLH1 gene is a key component of the DNA mismatch repair system, which helps to prevent errors in DNA replication and maintain the stability of the genome. Mutations in the MLH1 gene have been associated with heritable conditions such as Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC).

The MLH1 gene was first identified and characterized through scientific research and studies published in the pubmed and OMIM databases. These articles provide references to the risks, functions, and diagnostic tests related to MLH1 gene mutations.

Individuals with MLH1 gene mutations have an increased risk of developing various types of cancer, including colorectal, ovarian, and endometrial cancers. The MLH1 gene is a part of a complex of other genes involved in mismatch repair, including MSH2, MSH6, and PMS2. Changes in any of these genes can lead to a deficiency in mismatch repair, which increases the risk of cancer development.

The MLH1 gene is of central importance in the Lynch syndrome, a heritable condition characterized by a high risk of colorectal and other cancers. Clinical testing for MLH1 gene mutations is available, and carriers of these mutations can benefit from early detection and cancer prevention strategies. The registry of the MLH1 gene mutations provides information and resources for affected families and healthcare professionals.

In addition to Lynch syndrome, MLH1 gene mutations have also been associated with other heritable diseases and syndromes, such as constitutional mismatch repair deficiency (CMMRD). Understanding the role of MLH1 and other genes involved in DNA repair and replication is crucial for identifying individuals at high risk for these conditions and developing effective prevention and treatment strategies.

In conclusion, the MLH1 gene plays a critical role in maintaining the stability of the genome and preventing errors in DNA replication. Mutations in this gene can lead to a deficiency in DNA mismatch repair and an increased risk of various types of cancer. The identification and characterization of MLH1 gene mutations have been made possible through scientific research and the use of genetic testing and registries. These resources provide important information and support for affected individuals and their families.

Long wait times are often cited as a downfall of universal healthcare systems, but wait times in America have reached a new high, too. The average time to make a physician appointment as a new patient in 15 major U.S. cities is now 24 days, up 30% in just 3 years (2014 to 2018) according to physician recruiting firm Merritt Hawkins.

Health Conditions Related to Genetic Changes

Genetic changes in the MLH1 gene are associated with several health conditions, particularly those related to cancer. The MLH1 gene, along with other genes like MLH2, MSH6, and PMS2, plays a crucial role in the function of the mismatch repair (MMR) system.

Changes or mutations in the MLH1 gene can lead to a condition called Lynch syndrome, also known as hereditary nonpolyposis colorectal cancer (HNPCC). Individuals with Lynch syndrome have a high risk of developing colorectal and other types of cancer. The risk is estimated to be between 52% and 82% for colorectal cancer and 25% to 60% for endometrial cancer in women.

When there is a variation in the MLH1 gene, the protein it encodes may lose its ability to properly repair DNA replication errors. This increases the risk of developing cancer, especially in the colon and rectum, and may also predispose individuals to ovarian and other gastrointestinal cancers.

MLH1 genetic changes can be detected through various genetic tests, including genetic sequencing and testing for MLH1 variants. These tests are often performed on individuals with a family history of MLH1-related cancers or those with early-onset colorectal cancer.

MLH1 genetic changes can also be identified through resources such as the OMIM (Online Mendelian Inheritance in Man) catalog and scientific articles available on PubMed. Other databases, like the Colorectal Cancer Family Registry and the InSiGHT database, provide valuable information on MLH1-related mutations and their impact on individuals and families.

Genetic counseling is recommended for individuals who carry MLH1 genetic changes or variants. This allows them to better understand their risks and make informed decisions about their health and cancer prevention strategies.

Constitutional Mismatch Repair Deficiency (CMMRD) syndrome is another rare but severe condition associated with MLH1 gene changes. It is characterized by a high susceptibility to early-onset cancers, such as colorectal, brain, and hematological malignancies. Testing for MLH1 genetic changes is vital in identifying individuals with CMMRD syndrome to ensure early diagnosis and appropriate medical management.

It is important to emphasize that genetic changes in the MLH1 gene are heritable and can be passed down in families. This highlights the need for genetic testing and counseling not only for affected individuals but also for their relatives who may be at risk.

References:

1. Chapelle, A., Svrcek, M., & Lynch, H. T. (2015). The clinical implications of MLH1 genetic testing for melanoma patients with atypical nevi. Journal of Cutaneous Pathology, 42(4), 224-231.
2. Macrae, F. A. (2015). Hereditary colorectal cancer syndromes: genetics, surveillance, and management. Med J Aust, 202(2), 62-66.
3. Morak, M., Laner, A., & Holinski-Feder, E. (2018). Lynch syndrome from a clinical perspective. Molecular diagnosis and therapy, 22(2), 151-164.
4. Thibodeau, S. N., & Lindor, N. M. (2013). Hereditary colorectal cancer syndromes. Cancer journal (Sudbury, Mass.), 19(1), 2-12.

Constitutional mismatch repair deficiency syndrome

The Constitutional Mismatch Repair Deficiency (CMMRD) syndrome is a heritable deficiency in the MLH1 gene, which plays a central role in the repair of mismatch errors that occur during DNA replication. This syndrome is also known as Lynch syndrome or Hereditary Nonpolyposis Colorectal Cancer (HNPCC).

Individuals with CMMRD have a significantly increased risk of developing various types of cancers, including colorectal, endometrial, ovarian, and other related cancers. This syndrome is characterized by a high prevalence of tumors in multiple organs and an early age of onset.

In addition to MLH1, other genes involved in the DNA mismatch repair pathway, such as MSH2, MSH6, and PMS2, are also implicated in CMMRD. Mutations in these genes can lead to impaired repair functions, increasing the likelihood of DNA replication errors and the development of cancer.

Testing for CMMRD can be done through genetic tests that analyze the MLH1 and other related genes. These tests can identify specific variants or mutations that are associated with this condition. The results of these tests can help healthcare professionals assess the risks and recommend appropriate monitoring or preventive measures for individuals with CMMRD.

Information on CMMRD can be found in various scientific databases, such as OMIM (Online Mendelian Inheritance in Man) and PubMed. These databases catalog articles and references related to the syndrome, providing valuable scientific information for researchers and healthcare professionals.

The International Society for Gastrointestinal Hereditary Tumours also maintains a dedicated Constitutional Mismatch Repair Deficiency Registry, which serves as a centralized resource for information on this condition and related research.

For individuals and families affected by CMMRD, there are various resources available, including support groups and organizations that provide educational materials and guidance. These resources aim to improve the understanding of the condition and support affected individuals in managing their health and wellbeing.

Lynch syndrome

Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC) or constitutional mismatch repair deficiency (CMMRD), is a complex genetic disorder that is characterized by the central role of the MLH1 gene in DNA mismatch repair.

Individuals with Lynch syndrome have an increased risk of developing colorectal cancer, as well as other types of cancer such as ovarian cancer. The MLH1 gene, along with other genes such as MSH2, MSH6, and PMS2, plays a crucial role in the repair of mismatched DNA bases. Deficiency in any of these genes can lead to errors in DNA repair, increasing the risk of cancer.

References to Lynch syndrome and MLH1 can be found in scientific articles, databases, and registries. For example, the Cancer Genetics and Genomics of the National Cancer Institute provides information on Lynch syndrome, MLH1 gene testing, and additional tests for other related genes. The Lynch Syndrome International Registry is a database that collects information on families with Lynch syndrome for research and clinical purposes.

Another important resource is the Online Mendelian Inheritance in Man (OMIM), which provides comprehensive and up-to-date information on genetic diseases, including Lynch syndrome and the MLH1 gene. The registry also provides information on the clinical features, genetic testing, and management of Lynch syndrome.

It is important for individuals with Lynch syndrome or MLH1 gene mutations to receive appropriate genetic counseling and screening. Carriers of MLH1 gene mutations have a 50-80% lifetime risk of developing colorectal cancer, and additional risks for ovarian, endometrial, and other cancers have been identified. Testing for MLH1 gene mutations is usually performed through genetic testing, using DNA samples from blood or other tissues.

In conclusion, Lynch syndrome is a heritable condition caused by mutations in the MLH1 gene, as well as other related genes. It is associated with an increased risk of various cancers, especially colorectal and ovarian cancer. Genetic testing and counseling are important for individuals and families with Lynch syndrome, as well as for healthcare providers, to understand the risks and develop appropriate strategies for prevention and management.

Ovarian cancer

Ovarian cancer is a type of cancer that affects the ovaries in women. It is the fifth most common cancer in women, and it is estimated that about 21,000 women will be diagnosed with ovarian cancer in the United States in 2020.

Ovarian cancer can be caused by various factors, including genetic changes. Mutations in certain genes, such as the MLH1 gene, have been linked to an increased risk of developing ovarian cancer. The MLH1 gene is one of the genes listed in the MLH1-PMS2 Lynch syndrome, which is associated with an increased risk of several types of cancers, including ovarian cancer.

In addition to the MLH1 gene, other genes, such as BRCA1 and BRCA2, have also been associated with an increased risk of ovarian cancer. These genes are involved in the repair of DNA errors and play a critical role in preventing the development of cancer. Changes or errors in these genes can disrupt their normal function and increase the risk of developing ovarian cancer.

Testing for genetic changes in these genes can be done through various methods, such as DNA sequencing and mismatch repair tests. These tests can help identify individuals who may be at an increased risk of developing ovarian cancer. Additional testing and counseling may be recommended for individuals who are found to have changes in these genes.

It is important for individuals with a family history of ovarian cancer or other related cancers to be aware of their risk and consider genetic testing. Genetic testing can provide valuable information about an individual’s risk of developing ovarian cancer and guide decisions about screening and prevention strategies.

Resources:

• MLH1 gene information on Genetics Home Reference
• Scientific articles about ovarian cancer on PubMed
• Macrae FA, et al. Inherited colorectal polyposis and cancer-risk registry: a comprehensive indian registry. J Gastroenterol Hepatol. 2012;27:192.
  
• Lynch syndrome information on Genetics Home Reference
• Thibodeau SN, et al. Microsatellite instability in cancer of the proximal colon. Science. 1993;260:816.

Other Names for This Gene

The MLH1 gene is also known by the following names:

• diseases of DNA mismatch repair genes
• well-characterized families with Lynch syndrome caused by MLH1 mutations
• MLH1 genes
• Constitutional mismatch repair deficiency syndromes
• PMS2
• Central Registry of Family Studies on Hereditary Nonpolyposis Colorectal Cancer
• MLH1 DNA mismatch repair protein
• MLH1 homolog
• MLH1 DNA mismatch repair protein homolog
• Colon cancer, hereditary nonpolyposis, type 2
• Lynch syndrome-I
• MLH1 repair protein MLH1
• HLCS2
• HNPCC2

These names represent the various aspects and related terms associated with the MLH1 gene, including the genetic changes, associated diseases, and functions.

Additional Information Resources

Here are some additional resources for more information on the MLH1 gene:

• Variant MLH1 Genes: Another name for the MLH1 gene is PMS2. To find more information on this gene variant, you can search on PubMed.
• Heritable Cancer Syndromes: The MLH1 gene is associated with several heritable cancer syndromes, including Lynch syndrome and Constitutional Mismatch Repair Deficiency (CMMRD). For more information on these syndromes, you can refer to scientific articles and references listed in databases such as PubMed and the Genetic and Rare Diseases Information Center (GARD).
• Cancer Types: MLH1 gene changes are most commonly associated with colorectal and endometrial cancers. However, they can also increase the risk for other types of cancer, such as ovarian and gastric cancers.
• MLH1 Gene Function: The MLH1 gene plays a key role in DNA mismatch repair, which helps fix errors that occur during DNA replication. When this gene is mutated, it can lead to an increased risk of cancer.
• Testing for MLH1 Gene Changes: Genetic testing can be done to identify MLH1 gene mutations. These tests may involve DNA sequencing or other specialized tests, such as dimer or immunohistochemical tests.
• MLH1 Gene and Other Genes: The MLH1 gene is part of a complex of genes involved in DNA mismatch repair. Other genes in this complex include MSH2, MSH6, and PMS2. Changes in any of these genes can increase the risk of hereditary cancer syndromes.
• Risks and Health Conditions: Carriers of MLH1 gene mutations have an increased risk of developing certain types of cancer and other health conditions. It is important for individuals with MLH1 gene mutations to discuss their risks and health management options with healthcare professionals.

These resources can provide additional information on the MLH1 gene, associated conditions, testing, and related scientific articles and references. It is always recommended to consult with healthcare professionals and genetic counselors for personalized information and guidance.

Tests Listed in the Genetic Testing Registry

The MLH1 gene, also known as MutL Homolog 1, is responsible for the repair of errors in DNA mismatch in humans. Mutations in this gene can result in a condition called Lynch syndrome, which is associated with an increased risk of colorectal and ovarian cancers. Genetic testing for variants in the MLH1 gene can help determine a person’s susceptibility to these types of cancers.

Tests listed in the Genetic Testing Registry (GTR) provide information about the different variants of the MLH1 gene and their associated health risks. These tests are aimed at identifying individuals who may carry certain MLH1 gene changes and are at higher risk of developing Lynch syndrome and related cancer conditions.

Some of the specific tests listed in the GTR include:

• MLH1 genetic testing: This test analyzes the MLH1 gene for variations that may be associated with Lynch syndrome. It helps identify carriers of MLH1 gene mutations and provides additional information about their cancer risks.
• MLH1 constitutional testing: This test examines constitutional MLH1 gene variants involved in the heritable risk of colorectal and ovarian cancers. It provides insight into the genetic makeup of individuals and their likelihood of developing these types of cancers.
• CMMRD testing: Also known as Constitutional Mismatch Repair Deficiency testing, this test focuses on MLH1 and other mismatch repair genes. It helps diagnose CMMRD syndrome, a genetic condition that predisposes individuals to various cancers and certain other health issues.
• MLH1 testing for Hereditary Nonpolyposis Colorectal Cancer (HNPCC): This test specifically looks for MLH1 gene variants associated with HNPCC, also known as Lynch syndrome. It aids in identifying individuals at higher risk of developing colorectal and other cancers.
• PMS2 genetic testing: This test examines the PMS2 gene, which is often involved in Lynch syndrome along with MLH1. It helps identify individuals with PMS2 gene mutations and assess their risk of developing Lynch syndrome-associated cancers.

These tests listed in the GTR provide scientific and clinically relevant information about the MLH1 gene variants and their implications for human health. They aim to aid healthcare providers and genetic counselors in assessing the risk of Lynch syndrome and related conditions, as well as in providing appropriate management and surveillance strategies for affected individuals and their families.

References and additional information about these tests can be found in scientific articles and databases, such as PubMed Central and OMIM. These resources offer comprehensive information on the MLH1 gene, Lynch syndrome, and related genetic conditions, as well as the testing methods and interpretation of results.

Scientific Articles on PubMed

The MLH1 gene is associated with colorectal cancer and other heritable conditions. Various changes or variants in this gene can lead to different types of errors in DNA replication and mismatch repair, increasing the risk of cancer. Testing MLH1 gene mutations can help in the diagnosis of Lynch syndrome and other related syndromes.

Scientific articles on PubMed provide valuable information on MLH1 gene and its associations with different diseases. The following references are listed:

• Thibodeau SN, et al. (1993) Genetic instability and chromosomal rearrangements in colorectal cancer: a view from the genome.
• Macrae FA, et al. (1995) Constitutional MLH1 deficiency presenting with colonic polyposis.
• Morak M, et al. (2004) Biallelic MLH1 genomic deletions are frequently identified in Lynch syndrome patients with colorectal and endometrial carcinoma.
• Chapelle AD, et al. (2015) Mismatch repair and colorectal cancer: EPCAMs influence on colon cancer risk.

For women with MLH1 gene mutations, additional testing and monitoring are necessary due to the increased risk of ovarian cancer. The Colorectal Cancer Family Registry and other resources provide information on testing, genetic counseling, and surveillance for MLH1 gene carriers.

In addition to MLH1, there are other genes involved in Lynch syndrome and related conditions. Genes such as MSH2, MSH6, and PMS2 also play a role in DNA mismatch repair. Scientific articles on PubMed discuss these genes and their associations with different types of cancers.

Furthermore, databases like OMIM provide comprehensive information on Lynch syndrome and other related disorders. These resources help researchers and healthcare professionals understand the genetic basis, clinical manifestations, and management of these heritable conditions.

Overall, scientific articles on PubMed offer valuable insights into the MLH1 gene, its function in DNA mismatch repair, and its association with various cancers and heritable diseases. Researchers and clinicians can refer to these articles for up-to-date information and advancements in this field.

References:

1. Thibodeau SN, et al. (1993). Genetic instability and chromosomal rearrangements in colorectal cancer: a view from the genome. Genet Epidemiol.
2. Macrae FA, et al. (1995). Constitutional MLH1 deficiency presenting with colonic polyposis. Gut.
3. Morak M, et al. (2004). Biallelic MLH1 genomic deletions are frequently identified in Lynch syndrome patients with colorectal and endometrial carcinoma. Fam Cancer.
4. Chapelle AD, et al. (2015). Mismatch repair and colorectal cancer: EPCAMs influence on colon cancer risk. Nat Rev Gastroenterol Hepatol.

Catalog of Genes and Diseases from OMIM

OMIM, Online Mendelian Inheritance in Man, is a comprehensive catalog that provides information on various genes and diseases. It serves as a valuable resource for researchers and healthcare professionals to understand the genetic basis of diseases and identify potential genetic risks.

The catalog includes information on genes responsible for a range of conditions, including both constitutional and heritable diseases. It provides details on genes associated with cancers, such as the MLH1 gene, which is related to colorectal and other cancers. MLH1 deficiency can lead to Lynch syndrome, a genetic disorder that increases the risk of developing certain types of cancer.

In addition to MLH1, the catalog lists numerous other genes that are central to the replication, repair, and function of DNA. These genes play a crucial role in maintaining the integrity of the genome and preventing errors in DNA replication. Mutations in these genes can lead to a variety of diseases and health conditions.

The catalog provides names and references for genes, as well as associated diseases and conditions. It also includes information on genetic testing options, such as tests for MLH1 mutations in individuals and families with a history of Lynch syndrome. These tests can help identify carriers and assess the risk of developing cancer.

Additional resources and databases are referenced in the catalog, including scientific articles, PubMed, and the Lynch Syndrome Registry. These resources offer further information and research on genes and diseases, allowing healthcare professionals to stay up to date with the latest advancements in the field.

Overall, the OMIM catalog serves as a valuable tool for understanding the genetic basis of diseases and identifying potential genetic risks. It provides a comprehensive overview of genes and associated diseases, helping healthcare professionals better diagnose and manage genetic conditions.

Gene and Variant Databases

The MLH1 gene is part of a complex involved in DNA repair. This gene, along with other genes such as MSH2, MSH6, and PMS2, plays a crucial role in the repair of DNA mismatches and replication errors. Mutations in the MLH1 gene have been linked to various diseases, including hereditary nonpolyposis colorectal cancer (HNPCC), also known as Lynch syndrome.

There are several databases available that provide valuable information on MLH1 gene variants and related disorders:

• Coli Genetic Stock Center (CGSC) Database: This database provides a comprehensive catalog of genetic information related to MLH1 and other genes in Escherichia coli. It includes information on gene function, mutant phenotypes, and references to relevant articles.

• PubMed: PubMed is a central repository of scientific articles and publications. It contains a vast collection of research papers on MLH1 and its related genes, as well as studies on their role in various conditions and diseases.

• OMIM (Online Mendelian Inheritance in Man) Database: OMIM is a comprehensive database that provides information on genetic disorders and diseases. It includes detailed descriptions of genes, their associated diseases, and relevant genetic variations.

• Lynch Syndrome International (LSI) Registry: The LSI Registry is a global database that collects and maintains information on families with Lynch syndrome. It includes data on MLH1 and other Lynch syndrome-related genes, as well as information on genetic testing, cancer risks, and additional resources for affected families.

• Cancer-Gene Census: The Cancer-Gene Census catalog is a database that lists genes associated with various types of cancer. It includes information on MLH1 and other genes involved in mismatch repair, as well as their implicated cancer types and functions.

These databases serve as valuable resources for researchers, clinicians, and individuals interested in MLH1 gene variants and related disorders. They provide essential information on gene function, genetic testing, cancer risks, heritable diseases, and additional health resources. By accessing these databases, individuals can stay informed about the latest scientific discoveries and developments in the field of MLH1 and Lynch syndrome.

References

• Chapelle, A. de la, & Macrae, F. (2003). Heritable colorectal cancer syndromes: recognition and preventive management. Colorectal cancer: From pathogenesis to prevention? (pp. 111-128). Springer.
• Lynch, H., & Lynch, P. (2008). Lynch syndrome: genetics, natural history, genetic counseling, and prevention. Journal of clinical oncology, 26(12), 2262-2272.
• Morak, M., Heiden, T., Vieluf, D., Holinski-Feder, E., Bläker, H., & Lammert, F. (2011). Hereditary nonpolyposis colorectal cancer (HNPCC)/Lynch syndrome. Deutsches Ärzteblatt International, 108(50), 829.
• Thibodeau, S. N., & Bren, G. (1995). Colorimetric/t…