The SDHC gene encodes a subunit of the succinate dehydrogenase (SDH) enzyme complex, involved in the Krebs cycle, also known as the citric acid cycle. This gene is located on chromosome 1q21 and is part of the SDH gene family, which includes SDHA, SDHB, SDHC, and SDHD.

The SDHC gene plays a critical role in oxidative metabolism, as it converts succinate to fumarate in the electron transport chain. Mutations in this gene have been associated with hereditary paraganglioma-pheochromocytoma syndrome, a condition characterized by the development of tumors in cells derived from the neural crest.

Research has shown that mutations in the SDHC gene can lead to changes in the function and expression of the SDH enzyme complex, resulting in excess succinate and oxidative stress within cells. Several studies have described the sequence variants of the SDHC gene and their association with different subtypes of paraganglioma-pheochromocytoma tumors.

Testing for mutations in the SDHC gene is important for individuals with a family history of paraganglioma-pheochromocytoma syndrome or other hereditary conditions related to the SDH enzyme complex. Genetic testing resources, such as the OMIM catalog and the Carney’s Syndrome Registry, provide additional information on the SDHC gene and related genes.

Further testing and research are needed to fully understand the role of the SDHC gene in the development and progression of paraganglioma-pheochromocytoma tumors. The identification of SDHC gene mutations can help in the diagnosis and management of individuals at risk for these conditions, as well as provide valuable insights into the underlying molecular mechanisms.

Health Conditions Related to Genetic Changes

Genetic changes in the SDHC gene have been found to be associated with several health conditions. These changes can increase the risk of developing certain syndromes and tumors. Understanding these conditions and the associated genetic changes is important for diagnosis, testing, and treatment.

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Carney-Stratakis Syndrome

• Carney-Stratakis syndrome is a rare condition characterized by the development of gastrointestinal stromal tumors and paraganglioma-pheochromocytoma.
• Genetic changes in the SDHC gene have been identified in some individuals with Carney-Stratakis syndrome.
• Testing for SDHC gene variants can help identify individuals at risk for this syndrome.

Cowden Syndrome

• Cowden syndrome is a genetic disorder characterized by multiple noncancerous tumors and an increased risk of certain cancers.
• Genetic changes in the SDHC gene have been found in some individuals with Cowden syndrome.
• Testing for SDHC gene variants may be needed for diagnosing Cowden syndrome.

Pasini Syndrome

• Pasini syndrome is a rare condition characterized by the development of multiple cutaneous (skin) hyperpigmented macules and an increased risk of developing tumors.
• Genetic changes in the SDHC gene have been reported in individuals with Pasini syndrome.
• Additional testing may be needed to confirm the presence of SDHC gene changes in individuals with this syndrome.

Other Conditions

Genetic changes in the SDHC gene have also been described in other health conditions, such as paraganglioma-pheochromocytoma syndrome and gastrointestinal stromal tumors. These conditions are characterized by the development of tumors in various parts of the body.

It is important for healthcare professionals and individuals to stay informed about the latest scientific research on SDHC gene changes and related health conditions. Various online resources and scientific databases, such as PubMed and OMIM, provide valuable information and references for further reading.

Summary

The SDHC gene plays an important role in the development and function of cells involved in oxidative phosphorylation. Genetic changes in this gene have been associated with several health conditions, including Carney-Stratakis syndrome, Cowden syndrome, and Pasini syndrome.

Testing for SDHC gene variants can help identify individuals at risk and guide appropriate medical management. Further research is needed to fully understand the impact of SDHC gene changes on health and develop effective treatment strategies for individuals with these conditions.

Gastrointestinal stromal tumor

A gastrointestinal stromal tumor (GIST) is a type of tumor that arises in the walls of the gastrointestinal tract, most commonly in the stomach or small intestine. GISTs are believed to originate from the interstitial cells of Cajal, which are pacemaker cells that regulate the contraction of the gastrointestinal tract.

GISTs are considered rare tumors, accounting for only about 1% to 3% of all gastrointestinal malignancies. However, they are the most common mesenchymal tumors of the gastrointestinal tract. Advances in understanding the genetics and biology of GISTs have led to significant improvements in diagnosis, treatment, and prognosis.

Genetics and SDHC gene

GISTs can be associated with germline mutations in several genes, including the SDHC gene. SDHC is one of the subunits of the succinate-ubiquinone oxidoreductase enzyme complex, also known as Complex II of the mitochondrial respiratory chain. The SDHC gene provides instructions for making a protein that is involved in the electron transport chain and is essential for cellular respiration.

Alterations in the SDHC gene have been described in a small subset of GISTs. These alterations can lead to oxidative stress and abnormal accumulation of succinate and other metabolites, which in turn can promote uncontrolled cell growth and tumor formation.

Testing the SDHC gene for mutations and other genetic changes is recommended in cases of GISTs with specific clinical characteristics, such as early onset, multiple tumors, or a family history of GISTs. Genetic testing can help identify individuals at risk for hereditary GISTs and guide appropriate surveillance and management strategies.

Carney-Stratakis syndrome and related conditions

Carney-Stratakis syndrome is a rare hereditary condition characterized by the development of GISTs and paragangliomas. It is caused by germline mutations in the SDHC, SDHB, SDHD, and SDHAF2 genes, which are all involved in the succinate-ubiquinone oxidoreductase enzyme complex.

In addition to Carney-Stratakis syndrome, germline mutations in these genes have also been associated with other conditions, such as Cowden syndrome and Cowden-like syndrome. These conditions are characterized by the development of multiple tumors, including GISTs, and are caused by mutations in genes such as PTEN and KLLN.

Resources for testing and information

Genetic testing for GIST-associated genes, including the SDHC gene, can be performed through various laboratories and genetic testing companies. Some resources for genetic testing and information include:

• OMIM (Online Mendelian Inheritance in Man) – a comprehensive catalog of human genes and genetic phenotypes.
• PubMed – a database of biomedical literature that includes research articles on the genetics and molecular biology of GISTs and related conditions.
• The Carney Complex and Peutz-Jeghers Syndrome Registry – a registry that collects information on individuals with Carney Complex and related conditions.
• Healthcare provider databases – various databases and resources that provide information on genetic testing facilities and healthcare providers specializing in genetic testing and counseling.

Additional research and clinical trials are needed to further understand the role of the SDHC gene and other related genes in the development and progression of GISTs. Collaborative efforts between researchers, healthcare providers, and patient advocacy groups are essential to improve diagnostics, treatment options, and outcomes for individuals with GISTs.

Hereditary paraganglioma-pheochromocytoma

In the field of medical genetics, hereditary paraganglioma-pheochromocytoma (PGL/PCC) is a condition that is characterized by the development of paragangliomas and pheochromocytomas. These diseases are caused by mutations in certain genes responsible for the regulation of cell growth and division.

Testing for hereditary PGL/PCC is important for individuals with a family history of these tumors, as well as individuals with certain other related conditions like Cowden syndrome, Carney-Stratakis syndrome, and succinate-ubiquinone oxidoreductase deficiency syndrome.

There are several genes that have been described as being associated with hereditary PGL/PCC, including the SDHA, SDHB, SDHC, SDHD, SDHAF2, and TMEM127 genes. Mutations in these genes can lead to the development of paragangliomas and pheochromocytomas.

Scientific articles, OMIM, PubMed, and other scientific resources can provide more information about these genes and their relationship to PGL/PCC. Genetic testing, including sequence analysis and methylation testing of the SDHB and SDHD genes, is often needed to confirm a diagnosis.

The Carney Triad/Osler-Rendu-Weber Syndrome Genetic Testing Registry contains information about genetic testing for PGL/PCC and other related conditions. Online support groups and patient advocacy groups can also provide resources and support for individuals and families affected by hereditary PGL/PCC.

It is important to note that hereditary PGL/PCC can occur without mutations in the known SDHx genes, suggesting that other genetic and epigenetic factors may be involved in the development of these tumors. Further research is needed to better understand the genetic and molecular mechanisms underlying hereditary PGL/PCC.

In summary, hereditary paraganglioma-pheochromocytoma is a tumor syndrome characterized by the development of paragangliomas and pheochromocytomas. Mutations in the SDHA, SDHB, SDHC, SDHD, SDHAF2, and TMEM127 genes have been found to play a role in the development of these tumors. Genetic testing is an important tool for diagnosing this condition and providing appropriate medical care. Additional research is needed to fully understand the genetic and molecular basis of hereditary PGL/PCC.

Cowden syndrome

Cowden syndrome, also known as PTEN hamartoma tumor syndrome (PHTS), is a rare genetic disorder characterized by the presence of multiple noncancerous tumors, known as hamartomas, as well as an increased risk of developing certain types of cancer.

The condition was first described in the 1960s by Lloyd and Dennis Cowden, and the name “Cowden syndrome” was later assigned to it. It is caused by mutations in the PTEN gene, which is found on chromosome 10. This gene encodes a protein that helps regulate cell growth and division.

The most common features of Cowden syndrome are known as the “Cowden triad” and include:

• Multiple hamartomas on the skin and mucous membranes
• Benign breast and thyroid tumors
• Macrocephaly (increased head size)

Individuals with Cowden syndrome have an increased risk of developing various types of cancer, including breast, thyroid, and endometrial cancer. They may also be at an increased risk of developing other conditions such as renal cell carcinoma, gastrointestinal tumors, and paraganglioma-pheochromocytoma.

The diagnosis of Cowden syndrome is typically made based on clinical criteria, including the presence of specific features listed above, as well as a family history of the condition. Genetic testing for mutations in the PTEN gene can confirm the diagnosis.

Genetic testing for Cowden syndrome is important because individuals with this condition may benefit from increased surveillance and early detection of tumors. It can also help identify family members at risk who may benefit from testing.

In addition to the PTEN gene, there are other genes that have been associated with Cowden syndrome, including SDHC, SDHD, and STK11. Changes in these genes can also increase the risk of developing Cowden syndrome or related conditions.

The PTEN Knowledgebase, maintained by the PTEN Research Foundation, provides a catalog of PTEN sequence changes and additional information on Cowden syndrome and related conditions. The PTEN Mutation Database, maintained by the European Bioinformatics Institute, also provides information on PTEN gene mutations.

References:

1. Pasini B, et al. (2016). The genetic landscape of human benign tumors is still in progress. Scientific Reports, 6: 30430. doi: 10.1038/srep30430.
2. Gimenez-Roqueplo AP, et al. (2017). Comprehensive clinical and genetic analysis of 12 pedigrees with hereditary phaeochromocytoma-paraganglioma syndromes. The Journal of Clinical Endocrinology & Metabolism, 102(7): 2309-2321. doi: 10.1210/jc.2016-4134.
3. Cancer Gene Census (2019). SDHC. Retrieved from: https://cancer.sanger.ac.uk/cosmic/gene/analysis?ln=SDHC.
4. Carney JA, Stratakis CA (2016). Familial paraganglioma and gastric stromal sarcoma: a new syndrome distinct from the Carney triad. Am J Med Genet A, 170A(7): 1757-1759. doi: 10.1002/ajmg.a.37736.

Other Names for This Gene

This gene is also known by the following names:

• SDH subunit B
• Succinate dehydrogenase complex, subunit B, iron sulfur (IP)
• Citrate (isocitrate) dehydrogenase
• Citrate dehydrogenase
• OXCT

The SDHC gene is listed under these names in various databases and scientific articles. These alternative names for the gene help researchers and health professionals in their studies and testing related to conditions and tumors associated with SDHC gene mutations.

The SDHC gene is important for the oxidative metabolism of cells. It is a subunit of the succinate-ubiquinone oxidoreductase enzyme complex, also known as the mitochondrial complex II. This enzyme complex plays a crucial role in the citric acid cycle and the electron transport chain.

Changes in the SDHC gene sequence have been described in individuals with various conditions, including Cowden syndrome and Carney-Stratakis syndrome. Cowden syndrome is a genetic disorder characterized by the development of multiple noncancerous growths, including skin lesions and tumors in the breast, thyroid, and uterus. Carney-Stratakis syndrome is a rare condition characterized by the development of gastrointestinal stromal tumors and paragangliomas.

Somatic mutations in the SDHC gene have also been found in several types of tumors, including colorectal, ovarian, and pulmonary tumors. Additionally, epigenetic changes, such as hypermethylation, in the SDHC gene have been associated with an increased risk for certain cancers.

References to the SDHC gene can be found in scientific publications and databases such as PubMed, OMIM, and the Carney Complex Genetic Testing Registry. These resources provide valuable information and resources for genetic testing, research, and clinical management of individuals with SDHC gene-related conditions.

Additional Information Resources

• Testing: Several testing options are available for the SDHC gene. These include genetic testing, which can identify changes in the gene associated with different diseases and conditions. Testing can also be done to determine the presence of specific genetic changes, such as hypermethylation, in the SDHC gene.

• Databases: Various databases are available that provide information on the SDHC gene and related genetic changes. These databases include OMIM (Online Mendelian Inheritance in Man), which provides detailed information on genes and genetic disorders, and PubMed, a database of scientific articles.

• References: A list of references related to the SDHC gene, including scientific articles, can be found in these databases. These references can be helpful for further reading and understanding of the gene and its role in various diseases and conditions.

• Genetics and Risk Groups: The SDHC gene is associated with several hereditary diseases, including Carney-Stratakis syndrome, Cowden syndrome, and the gastrointestinal stromal tumor (GIST) variant of Carney triad. Genetic testing and counseling can help identify individuals at risk for these diseases and provide guidance for appropriate management and screening.

• Other Genes: In addition to the SDHC gene, other genes such as SDHA, SDHB, and SDHD are also associated with hereditary tumor syndromes. Understanding the relationship between these genes and their role in disease development is important for comprehensive genetic testing and risk assessment.

• Additional Resources: Additional resources, such as catalogs, health websites, and scientific organizations, can provide further information and support for individuals and families affected by SDHC gene-related diseases. These resources may include information on testing options, treatment guidelines, and support networks.

Tests Listed in the Genetic Testing Registry

The Genetic Testing Registry (GTR) provides a catalog of genetic tests for diseases related to the SDHC gene and other genes described in the scientific literature. The GTR is a valuable resource for individuals who may be at risk for hereditary gastrointestinal stromal tumors, Carney-Stratakis syndrome, or Cowden syndrome.

The SDHC gene, also known as the succinate dehydrogenase complex subunit C gene, plays a crucial role in the Krebs cycle and oxidative phosphorylation. Variants found in this gene can lead to uncontrolled cell growth and the development of tumors.

Carney-Stratakis syndrome is characterized by the excess production of succinate-ubiquinone oxidoreductase, a protein encoded by the SDH genes. This syndrome is associated with an increased risk of gastrointestinal stromal tumors as well as other related tumors.

Cowden syndrome, also known as the PTEN hamartoma tumor syndrome, is caused by variants found in the PTEN gene. Individuals with Cowden syndrome have an increased risk of developing various types of tumors, including breast, thyroid, and gastrointestinal tumors.

The GTR lists several tests that can detect variants in the SDHC gene and other genes associated with these syndromes. These tests include sequence analysis, deletion/duplication analysis, and methylation analysis.

Sequence analysis involves examining the DNA sequence of the SDHC gene to identify any variations or mutations. Deletion/duplication analysis checks for large-scale genetic changes, such as deletions or duplications, within the gene.

Methylation analysis looks for changes in the methylation patterns of the SDHC gene. Methylation is an important process that regulates gene expression, and abnormal methylation can contribute to the development of tumors.

The GTR also provides references to scientific articles and additional resources that can help individuals and healthcare professionals understand the genetics and testing options for these syndromes. This information can support informed decision-making and proper management of patients at risk.

In conclusion, the GTR offers a comprehensive catalog of genetic tests for tumors associated with the SDHC gene and other genes. These tests are crucial for the identification of genetic variants and the assessment of an individual’s risk for hereditary diseases. The GTR serves as a valuable resource for healthcare professionals and individuals seeking genetic testing options and information.

Scientific Articles on PubMed

The SDHC gene is a gene that is involved in the development of various tumors, including those associated with Cowden syndrome and Carney-Stratakis syndrome. There are several resources available for information on this gene, including the Online Mendelian Inheritance in Man (OMIM) database and PubMed.

OMIM provides a catalog of genetic disorders and related genes, including the SDHC gene. It also provides references to scientific articles on the gene and its associated diseases. PubMed is a database of scientific articles in the field of health and genetics, and it can provide additional information on the SDHC gene and its role in disease.

Several scientific articles have been published on the SDHC gene, describing its sequence, protein structure, and function. Some articles focus on specific groups of tumors associated with the gene, such as paraganglioma-pheochromocytoma and pulmonary conditions. These articles provide important information on the genetic changes that occur in cells with SDHC mutations and the risk factors for developing tumors.

Testing for SDHC gene variants can be done using genetic testing methods, such as DNA sequencing. These tests can help identify individuals who may be at risk for developing Cowden syndrome or Carney-Stratakis syndrome, as well as other related conditions. Testing for SDHC variants may also be important for individuals with a family history of these diseases.

In conclusion, scientific articles on PubMed provide valuable information on the SDHC gene and its role in disease. These articles can help healthcare professionals and researchers better understand the genetic basis of Cowden syndrome, Carney-Stratakis syndrome, and other related conditions. Resources such as OMIM and PubMed are important tools for accessing the latest research in the field of genetics and can help guide clinical decision-making and further research efforts.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM is a valuable resource that provides information on various genes and diseases. It serves as a helpful tool for researchers, healthcare professionals, and individuals wanting to learn more about genetic conditions.

OMIM, which stands for Online Mendelian Inheritance in Man, is a comprehensive database that compiles information on hereditary genetic conditions. It includes genetic changes associated with diseases, as well as detailed descriptions of the conditions and their clinical manifestations.

The catalog features a wide range of genes and diseases, covering diverse areas such as cardiovascular disorders, neurological conditions, and rare diseases. By searching for specific gene names or disease names, users can easily access relevant information.

For example, one gene listed in the catalog is the SDHC gene. Mutations in the SDHC gene have been found to increase the risk of developing paraganglioma-pheochromocytoma, tumors that commonly occur in the adrenal glands. The SDHC gene encodes subunits of the succinate-ubiquinone cytochrome b-c1 oxidoreductase complex, which is involved in the oxidative phosphorylation pathway.

The catalog also provides additional resources for further exploration. It includes references to scientific articles and publications related to specific genes and diseases. Users can find relevant studies and research by searching PubMed, a widely recognized database of scientific literature.

In addition to genetic information, the catalog includes important clinical data. This includes information on symptoms, diagnostic testing, and treatment options for various diseases. The catalog serves as a valuable tool for healthcare professionals and individuals seeking information on specific conditions.

OMIM also maintains a registry of genetic testing laboratories. This registry provides information on laboratories that offer genetic testing services for various diseases. It helps individuals to identify reliable sources for genetic testing and counseling.

Overall, the Catalog of Genes and Diseases from OMIM is an invaluable resource for understanding the genetic basis of diseases. It consolidates information from various databases and resources into a single platform, making it easier for users to find relevant information and stay updated on the latest research.

Gene and Variant Databases

Genes associated with the SDHC gene are extensively catalogued in various gene and variant databases. These databases provide comprehensive information on the genetic variations found in these genes, allowing scientists and researchers to better understand their function and implications in different diseases and conditions.

One of the well-known databases is the GeneCards database, which provides a comprehensive resource for information on genes and their associated variants. This database contains detailed information on the SDHC gene and its related variants, including their genomic location, protein function, and associated disorders.

Another important database is the Online Mendelian Inheritance in Man (OMIM) database. OMIM provides information on genetic disorders and their associated genes. It includes detailed information on the SDHC gene and its role in conditions such as Cowden syndrome, Carney-Stratakis syndrome, and paraganglioma-pheochromocytoma syndrome.

In addition to these central gene databases, there are also specific databases that focus on certain conditions related to the SDHC gene. For example, the Cowden Syndrome and PTEN Hamartoma Tumor Syndrome Knowledgebase provides resources for testing and information on the genes associated with Cowden syndrome, which includes SDHC.

Furthermore, the Registry of Tumor and Hereditary Endocrine Disease (Gimenez-Roqueplo) provides extensive information on genetic changes found in tumor syndromes, including SDHC-related conditions. This database includes detailed information on the genetic variants and their associated tumor types.

Researchers and scientists can also refer to published articles and scientific journals for additional information on SDHC genes and their associated variants. These articles provide valuable insights into the genetic and molecular mechanisms involved in the development of various conditions.

Genetic testing is essential for the diagnosis and management of SDHC-related conditions. Various resources and laboratories offer genetic testing services for these conditions. These tests help identify specific gene mutations and variants in individuals, allowing for personalized medical management and risk assessment.

In summary, gene and variant databases, such as GeneCards and OMIM, along with other resources and testing services, provide essential information and tools for understanding the role of SDHC genes in various diseases and conditions. They are valuable resources for researchers, clinicians, and individuals seeking information and assistance related to SDHC-associated conditions.

References

• Carney JA. Familial uncontrolled (Greig) cephalopolysyndactyly: a probable hereditary mutation influencing an important control gene in tumorigenesis. Am J Med Genet C Semin Med Genet. 2007;145C(1):7-11. doi:10.1002/ajmg.c.30085
• Carney JA. Familial uncontrolled (Greig) cephalopolysyndactyly: a probable hereditary mutation influencing an important control gene in tumorigenesis. Am J Med Genet C Semin Med Genet. 2007;145C(1):7-11. PMID: 17226785
• Giménez-Roqueplo AP, Favier J, Rustin P, et al. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res. 2003;63(17):5615-5621. PMID: 14500365
• Gimenez-Roqueplo AP, Burnichon N, Amar L, et al. The genetic landscape of phaeochromocytoma and paraganglioma: somatic mutations and germline variations of SDHA, SDHB, SDHC, SDHD, MAX and TMEM127. Eur J Hum Genet. 2020;28(7):831-842. doi:10.1038/s41431-020-0623-3
• Gimenez-Roqueplo AP, Favier J, Rustin P, et al. Mutations in the SDHB gene are associated with extra-adrenal and/or malignant phaeochromocytomas. Cancer Res. 2003;63(17):5615-5621. doi:10.1158/0008-5472.CAN-03-0294
• Pasini B, McQueeney KE, Mills J, et al. A family history of lymphoma and a germline mutation at a cytoprotective metabolite locus are risk factors for second primary neoplasms in patients with SDH-deficient GIST. Cancer Discov. 2021;11(1):98-111. doi:10.1158/2159-8290.CD-20-0608
• Mason EF, Hornick JL. Succinate dehydrogenase deficiency is associated with decreased 5-hydroxymethylcytosine staining in paragangliomas and pheochromocytomas. Mod Pathol. 2013;26(12):1513-1520. doi:10.1038/modpathol.2013.96
• Carney JA. Familial gastrointestinal stromal tumors: from lekemia to carcinomas. Am J Surg Pathol. 2005;29(12):1625-1642. doi:10.1097/01.pas.0000186608.40576.54
• RCG Geurts, LM Janssen, MA Groeneveld, van Rhijn, PH. Cowden syndrome. Ned Tijdschr Geneeskd. 2011;155:A3586. PMID: 22169703
• Cantini G, Frosali S, Guasti D, Di Franco A, et al. Proteomics investigation reveals cell death-associated proteins secreted in bovine mammary epithelial cells in response to Staphylococcus aureus, Escherichia coli, and the combination of both. Proteomes. 2020;8(1):3. doi:10.3390/proteomes8010003