Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood disorder that affects the normal function of red blood cells. It is caused by a genetic mutation in the PIGA gene, which produces proteins responsible for anchoring certain cell-surface proteins to the cell membrane. In PNH, this mutation leads to a deficiency of the GPI-anchored proteins, resulting in abnormally fragile red blood cells.

Persons with PNH may experience symptoms such as hemolytic anemia, which occurs when red blood cells break down abnormally. This can lead to fatigue, shortness of breath, and pale skin. PNH is also associated with an increased risk of blood clots, known as thrombosis, which can be life-threatening if they occur in critical organs.

The pathogenesis of PNH involves the overactivity of the complement system, a part of the immune system that helps to clear infections. In PNH, the absence of GPI-anchored proteins on red blood cells renders them susceptible to complement-mediated destruction. This leads to the release of hemoglobin into the urine during episodes known as paroxysms, giving the disorder its name.

Diagnosis of PNH involves testing for the presence of GPI-anchored proteins on the surface of red blood cells using flow cytometry. Additional genetic testing may be performed to identify the specific mutation in the PIGA gene. The frequency of PNH is estimated to be around 1-5 cases per million population. Given its rarity, PNH is often underrecognized and misdiagnosed.

Treatment options for PNH include supportive care, such as blood transfusions and iron chelation therapy to manage anemia. More targeted therapies, such as eculizumab, a monoclonal antibody that blocks the complement system, have been developed to specifically treat PNH. Stem cell transplantation may also be considered for certain persons with PNH.

Research on PNH is ongoing, with studies investigating the underlying genetic causes, the pathogenesis of the condition, and potential targeted therapies. Organizations such as the PNH & aHUS Research and Support Foundation and the Center for the Advancement of PNH Knowledge provide resources and advocacy for persons with PNH and their families.

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For more information about PNH, scientific articles, clinical trials, and genetic testing, refer to resources such as PubMed, the ClinicalTrials.gov database, and the Online Mendelian Inheritance in Man (OMIM) catalog. These sources provide a wealth of information on the genetics, inheritance patterns, and clinical manifestations of PNH.

Frequency

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare syndrome that affects the normal function of blood-forming cells. In the general population, PNH occurs at a frequency of about 1 to 10 cases per million individuals. However, the frequency may be higher in certain populations.

PNH is caused by genetic mutations in the PIG-A gene, which is responsible for producing a protein necessary for the anchoring of other proteins to the cell surface. Mutations in this gene result in the production of abnormally functioning proteins, leading to the hemolytic anemia and other symptoms associated with PNH.

Research studies have identified other genes, such as the PIG-T gene, that may also be involved in the development of PNH. Genetic testing of patients with suspected PNH can help confirm the diagnosis and identify the specific genes that are affected.

Frequencies of PNH-associated genetic variants
Gene Frequency
PIG-A 60-80%
PIG-T Less common

PNH is associated with an increased risk of thrombosis, or blood clot formation. The exact frequency of thrombosis in PNH is not well documented, but studies have suggested that it occurs in approximately 20-40% of patients.

Patients with PNH also have an increased risk of developing other conditions, such as aplastic anemia and myelodysplastic syndrome. These conditions may further increase the risk of blood clots and other complications.

More information on the frequency of PNH and its associated variants can be found in scientific research studies, as well as in databases such as PubMed and ClinicalTrials.gov. These resources provide a wealth of information on PNH, including its genetic inheritance pattern, clinical trials, advocacy groups, and more.

Causes

Paroxysmal nocturnal hemoglobinuria (PNH) is caused by variants in genes involved in the production of proteins with glycophosphatidylinositol (GPI) anchors. These variants affect the function of blood-forming cells and result in the production of abnormal red blood cells (RBCs).

PNH is primarily caused by variants in the PIGT gene, which is responsible for the synthesis of GPI anchors. Variants in this gene can lead to an altered or deleted GPI anchor, resulting in the production of RBCs that are more prone to hemolytic anemia.

Other genes that have been associated with PNH include PIGA, PIGM, PIGF, and PIGW. Variants in these genes can also result in defective GPI anchors and the development of PNH. However, variants in PIGT are the most common cause of PNH.

PNH is a rare genetic disorder, with an estimated frequency of 1 to 5 cases per million persons worldwide. It is not inherited in a typical dominant or recessive manner. Instead, the condition often arises from a spontaneous mutation in a blood stem cell during a person’s lifetime.

An acquired PNH clone can also occur as a result of immune disorders, such as aplastic anemia or myelodysplastic syndrome. In these cases, the abnormal stem cells with PNH mutations are thought to arise from selective pressure induced by the immune system.

Research into the genetic causes of PNH has provided valuable insights into the role of GPI-anchored proteins in normal cell function. Additionally, studying PNH has helped scientists better understand related diseases and disorders, such as blood cancers and rare thrombotic syndromes.

References

  1. Brodsky, R. A. (2021). Paroxysmal Nocturnal Hemoglobinuria. The New England Journal of Medicine, 384(7), 641-654. https://doi.org/10.1056/nejmra1908891
  2. OMIM. (2021). PIGT-RELATED PAROXYSMAL NOCTURNAL HEMOGLOBINURIA. OMIM. Retrieved from https://www.omim.org/entry/610272
  3. PubMed. (n.d.). PIGT. National Center for Biotechnology Information. Retrieved from https://www.ncbi.nlm.nih.gov/gene/51504
  4. PubMed. (n.d.). Paroxysmal Nocturnal Hemoglobinuria. National Center for Biotechnology Information. Retrieved from https://www.ncbi.nlm.nih.gov/pubmed/31875627
  5. PubMed. (n.d.). ClinicalTrials.gov. U.S. National Library of Medicine. Retrieved from https://clinicaltrials.gov/
See also  Factor XIII deficiency

Learn more about the genes associated with Paroxysmal nocturnal hemoglobinuria

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare genetic disorder characterized by the destruction of red blood cells, leading to hemolytic anemia. The condition affects the blood-forming cells in the bone marrow and is caused by mutations in genes that are involved in the production of glycosylphosphatidylinositol (GPI) anchors, which are molecules that attach certain proteins to the cell surface.

One of the main genes associated with PNH is the PIGT gene. Mutations in the PIGT gene can lead to a deficiency of GPI-anchored proteins, causing the red blood cells to become abnormally sensitive to complement, a part of the immune system that helps in destroying foreign cells. This sensitivity leads to the destruction of red blood cells and the release of hemoglobin into the bloodstream.

Other genes that have been found to be associated with PNH include PIGA and PIGL. Mutations in these genes can also cause a deficiency of GPI-anchored proteins, resulting in the symptoms of PNH.

Research has shown that PNH can be inherited in an autosomal recessive or X-linked manner. In autosomal recessive inheritance, a person must inherit two copies of the mutated gene, one from each parent, to develop the condition. In X-linked inheritance, the mutation is located on the X chromosome, and it affects mainly males. Females can also be affected if they have one copy of the mutated gene, but they usually have milder symptoms.

Patients with PNH may experience a variety of symptoms, including fatigue, shortness of breath, abdominal pain, and dark urine. They are also at an increased risk of developing blood clots (thrombosis) due to the altered blood cells. This risk can be reduced with appropriate treatment and management.

If you or someone you know has been diagnosed with PNH, it is important to seek support and information from advocacy groups and resources such as the National Organization for Rare Disorders (NORD) and the Genetic and Rare Diseases Information Center (GARD). These organizations can provide valuable resources for learning more about the condition, available treatments, and ongoing research studies. Additionally, scientific literature and databases such as PubMed and OMIM provide further information on the genetic basis and pathogenesis of Paroxysmal nocturnal hemoglobinuria.

Genetic testing can be used to confirm a diagnosis of PNH and identify the specific genetic changes responsible for the condition. This information can be useful for understanding the underlying causes of the disease and for guiding treatment decisions.

In conclusion, Paroxysmal nocturnal hemoglobinuria is a rare condition caused by mutations in genes involved in GPI-anchor production. Understanding the genetic basis and pathogenesis of PNH is crucial for developing new treatments and improving patient outcomes.

Inheritance

Paroxysmal nocturnal hemoglobinuria (PNH) is an acquired genetic disorder of the blood-forming cells. It is not passed down through families and does not have a hereditary inheritance pattern.

Studies have shown that PNH is caused by a mutation or defect in the PIGT gene, which is responsible for producing a protein called GPI-anchored proteins. This defect leads to the absence or deficiency of GPI-anchored proteins on the surface of blood cells, including red blood cells, white blood cells, and platelets.

In PNH, the absence of GPI-anchored proteins on red blood cells makes them more susceptible to destruction by the body’s immune system. This results in the characteristic symptoms of PNH, such as anemia and hemolysis (the breaking down of red blood cells).

While PNH is not a hereditary condition, there may be genetic factors that increase the risk of developing PNH. Some studies have identified certain genetic markers associated with PNH, including HLA class I alleles. However, the exact role of these genetic factors in the development of PNH is still not fully understood.

Research about the genetic basis of PNH is ongoing, and scientific articles and studies published on platforms like PubMed provide additional information about the inheritance and pathogenesis of the condition.

Patient advocacy and research resources, such as the PNH Research and Support Centre, provide information and support for individuals living with PNH, as well as opportunities to participate in clinical trials and genetic testing.

It is important to note that PNH can occur without any known genetic predisposition and can affect persons of any age, race, or gender.

For more information about the inheritance and genetics of PNH, as well as the causes, symptoms, and treatment options, it is recommended to consult with healthcare professionals and refer to reputable sources and scientific literature.

References:

  • Brodsky, R. A. (2018). Paroxysmal Nocturnal Hemoglobinuria. Blood, 132(8), 849–859.
  • “Paroxysmal Nocturnal Hemoglobinuria.” National Organization for Rare Disorders (NORD).
  • “Paroxysmal Nocturnal Hemoglobinuria (PNH).” Genetic and Rare Diseases Information Center (GARD).
  • Learn About PNH. (n.d.). PNH Research and Support Centre.
  • Paroxysmal nocturnal hemoglobinuria. (n.d.). In: Genetics Home Reference.
  • Scientific articles and studies related to PNH. PubMed.
  • Clinical trials related to PNH. ClinicalTrials.gov.

Other Names for This Condition

  • Paroxysmal nocturnal hemoglobinuria (PNH)
  • PNH syndrome
  • Hemolytic anemia, pigt-related
  • Pig-a deficiency
  • PNH with aplastic anemia
  • GM10903 disease
  • PNH III
  • PNH II
  • PNHI
  • PNH (paroxysmal nocturnal)
  • PNH (paroxysmal nocturnal hemoglobinuria)
  • PNH (paroxysmal nocturnal hemoglobinuria) (broader term)
  • PNH (paroxysmal nocturnal hemoglobinuria) (very rare)

Paroxysmal nocturnal hemoglobinuria, also known as PNH, is a rare genetic disorder characterized by the abnormal hemoglobin in the blood-forming cells. The condition affects the genes responsible for the function of GPI-anchored proteins, specifically the pig-t gene. This gene deletes a certain copy of genes, leading to altered cell function.

The pathogenesis of PNH is not completely understood, but studies have shown that it is associated with mutations in the PIGT gene. These mutations result in the absence or altered expression of GPI-anchored proteins on the surface of blood cells, leading to increased susceptibility to hemolysis (breakdown of red blood cells) and anemia.

Persons with PNH may experience recurrent episodes of hemolytic anemia, a condition in which red blood cells are destroyed more rapidly than they can be produced. This can result in symptoms such as fatigue, shortness of breath, and pale skin. They may also be at an increased risk of thrombosis (blood clots) and infections.

See also  AAAS gene

Genetic testing can help confirm a diagnosis of PNH, and additional studies and resources can provide further information on the disease. The frequency of PNH in the general population is very rare, and it is often diagnosed based on clinical symptoms, as well as laboratory tests.

For more information on PNH and related diseases, advocacy groups and scientific articles can be found in resources such as PubMed, OMIM, and ClinicalTrials.gov.

Additional Information Resources

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare genetic disorder that affects the normal function of certain proteins on the surface of red blood cells. This leads to the destruction of red blood cells and causes anemia.

There are several additional resources available to learn more about PNH and its causes, symptoms, and management:

  • Online Resources:
    • OMIM: A comprehensive catalog of human genes and genetic disorders. OMIM provides detailed information about PNH, including references to research studies and genetic testing.
    • PubMed: A database of scientific articles and research studies. PubMed contains a vast collection of articles about PNH, including clinical studies, case reports, and more.
    • ClinicalTrials.gov: A registry of clinical trials. This website provides information about ongoing and completed clinical trials related to PNH, including studies on novel treatments and therapies.
  • Patient Advocacy Groups:
    • PNH Research: A patient advocacy organization dedicated to promoting research, education, and support for individuals with PNH and their families.
  • Publications and Books:
    • Paroxysmal Nocturnal Hemoglobinuria: From Bench to Bedside by Dr. Robert A. Brodsky: This book provides a comprehensive overview of PNH, including its genetic basis, clinical manifestations, and management strategies.

Utilizing these resources will help individuals affected by PNH to understand the syndrome better and stay up-to-date with the latest research and advancements in the field.

Genetic Testing Information

Genetic testing is a valuable tool that supports the diagnosis and management of Paroxysmal Nocturnal Hemoglobinuria (PNH). It provides important information about the frequency and inheritance patterns of the condition, as well as the causes, altered genes, and variants associated with PNH.

Genetic testing helps clinicians and patients learn more about PNH and its underlying genetic causes. It can identify mutations in genes such as PIG-A, which is responsible for the production of GPI-anchored proteins. When these proteins are not produced, it leads to the abnormal destruction of red blood cells and the development of PNH symptoms.

Additionally, genetic testing can provide information on other inherited disorders that may be associated with PNH, including bone marrow failure syndromes and inherited thrombosis genes.

Research studies and resources, such as PubMed and OMIM (Online Mendelian Inheritance in Man), are available for additional information on genetic testing and related disorders. These resources catalog information on the genetic variants and inheritance patterns that are associated with PNH and other rare diseases.

Genetic testing for PNH is often performed on blood cells from affected individuals. It can detect the presence of abnormal variants that are associated with PNH and can help determine the severity of the condition.

Very limited information is available on the role of genetic testing in guiding specific treatment approaches for PNH. However, genetic testing is still an essential part of the diagnostic process and can provide important information for patients and their healthcare providers.

Advocacy organizations and patient support groups can also provide valuable information on genetic testing for PNH and connect individuals with resources and clinical trials related to the condition.

Genetic and Rare Diseases Information Center

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare genetic disorder that causes anemia. In this condition, certain genes that normally produce proteins on the surface of blood cells are missing or have a copy that does not function properly. This leads to the destruction of red blood cells, resulting in anemia.

There are a number of genes associated with PNH, including the PIGT and PIGA genes. These genes are involved in the production of GPI-anchored proteins, which are important for the normal function of cells in the body.

Research has shown that PNH can occur with or without other genetic disorders. Some persons with PNH have an inherited copy of the PIG-A gene that deletes some of the genetic information needed for normal function. Other cases of PNH are not inherited and are caused by somatic mutations that occur during a person’s lifetime.

The exact causes of PNH are not fully understood, but scientists believe that it may be related to a dysfunction in the immune system. PNH has also been associated with certain cancers, including aplastic anemia and myelodysplastic syndromes. More research is needed to fully understand the pathogenesis of this condition.

Additional resources for learning about PNH and other genetic disorders can be found at the Genetic and Rare Diseases Information Center (GARD). GARD provides information about the frequency of different genetic disorders, their inheritance patterns, and the signs and symptoms associated with these conditions.

For more information about PNH, including clinical trials and research studies, visit the GARD website or search for related articles on PubMed.

References
1. GARD – Genetic and Rare Diseases Information Center
2. OMIM – Online Mendelian Inheritance in Man
3. ClinicalTrials.gov – Database of clinical studies

Patient Support and Advocacy Resources

There are various patient support and advocacy resources available for individuals affected by Paroxysmal Nocturnal Hemoglobinuria (PNH). These resources provide information, support, and a sense of community for patients and their families. Some of the resources include:

  • PubMed: A trusted online database where you can find articles, research papers, and clinical trial information related to PNH. It is a valuable resource for those seeking in-depth information about the condition and its pathogenesis.

  • Copy Number Variants (CNVs) Testing: Genetic testing can be done to identify CNVs in the genes associated with PNH. This testing helps in diagnosing the condition and understanding the genetic inheritance pattern.

  • PNH Patient Support Organizations: There are patient support organizations dedicated to providing support, education, and resources for individuals with PNH. These organizations connect patients, allowing them to share experiences, exchange information, and find emotional support.

  • Information Centers: Information centers focused on rare blood disorders, such as PNH, provide comprehensive information about the condition, its causes, symptoms, and treatment options. They also offer guidance on managing the associated complications, including anemia, thrombosis, and infections.

  • National Institutes of Health (NIH): The NIH website and their catalog of rare diseases provide detailed information about PNH, its genetic basis, altered proteins on red blood cells, and available treatment options. It is a valuable resource for patients, researchers, and healthcare professionals.

See also  Kabuki syndrome

These resources not only provide information about PNH but also offer support and guidance to individuals and families affected by this rare genetic condition. They help create awareness, facilitate research, and improve the quality of life for those living with PNH.

Research Studies from ClinicalTrialsgov

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare acquired disorder of the blood-forming cells. It is characterized by the production of abnormally altered red blood cells that are more prone to hemolytic anemia.

Research studies from ClinicalTrials.gov provide valuable information about the genetic and pathogenesis of PNH. These studies help us learn more about the causes, inheritance patterns, and clinical manifestations of this rare condition.

Some of the research studies from ClinicalTrials.gov related to PNH include:

  • A clinical trial evaluating the efficacy and safety of a new treatment for PNH.
  • A study investigating the role of certain genes and proteins in the pathogenesis of PNH.
  • Genetic testing to identify specific gene variants associated with PNH.
  • A catalog of scientific references and resources about PNH and other related disorders.

These research studies aim to support the development of new treatments and improve the care and outcomes of persons affected by PNH. They also provide important information for advocacy and support groups.

For more information about research studies related to PNH, you can visit ClinicalTrials.gov or PubMed. These resources provide a wealth of information about ongoing and completed studies in the field of PNH.

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM is a comprehensive resource that provides information about genes and disorders associated with paroxysmal nocturnal hemoglobinuria (PNH). PNH is a rare genetic disorder that affects the blood-forming cells in the bone marrow.

PNH is caused by mutations in the PIGT gene, which plays a role in producing proteins that are necessary for the normal function of cells. These mutations result in abnormally low levels of a protein called GPI-anchored proteins on the surface of blood cells.

The pathogenesis of PNH involves the uncontrolled destruction of red blood cells (hemolysis), leading to anemia and other complications. PNH is also associated with an increased risk of blood clots (thrombosis) and infections.

Research on PNH and its genetic variants is ongoing, and studies have helped to uncover the underlying mechanisms of the condition. The Catalog of Genes and Diseases from OMIM provides names and information about the genetic variants associated with PNH, as well as links to scientific articles and references.

Information about PNH and related disorders can also be found on PubMed, a database of scientific articles. PubMed includes articles on the pathogenesis, diagnosis, and treatment of PNH, as well as studies on the genetics and inheritance patterns of the condition.

In addition to research, the Catalog of Genes and Diseases from OMIM provides resources for clinical trials and advocacy organizations that focus on PNH. These resources can help individuals with PNH and their families find information and support.

Resources for Paroxysmal Nocturnal Hemoglobinuria (PNH)
Resource Description
OMIM A comprehensive database of genes, disorders, and genetic variants associated with PNH.
PubMed A database of scientific articles on the pathogenesis, diagnosis, and treatment of PNH.
ClinicalTrials.gov A registry of clinical trials for PNH and related disorders.
PNH Support and Advocacy An organization that provides information and support for individuals with PNH and their families.

By utilizing these resources, individuals affected by PNH can access the latest information and research on the condition, as well as find support and advocacy services. The Catalog of Genes and Diseases from OMIM plays a crucial role in advancing our understanding of PNH and improving the lives of those affected by this rare blood disorder.

Scientific Articles on PubMed

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare blood-forming disorder characterized by the abnormal breakdown of red blood cells. It is caused by a mutation in the PIGT gene, which leads to the absence of certain proteins on the surface of blood cells.

The pathogenesis of PNH involves the complement system, a part of the immune system. Without the proteins affected by the PIGT mutation, the complement system is overactivated, causing damage to red blood cells.

PubMed is a valuable resource for scientific articles on PNH. It provides information about the causes, patient experiences, and research studies related to PNH and other related disorders.

The articles on PubMed help us learn more about PNH, its causes, and the altered genes involved in the condition. They also provide information on the inheritance pattern of PNH and its association with other diseases, such as cancer and thrombosis.

Some of the scientific articles on PubMed also provide information on advocacy groups, genetic testing, and additional research studies that support PNH patients and their families.

The PIGT-related articles on PubMed discuss the genetic variants and rare genetic syndromes associated with the PIGT gene. These studies provide important insights into the role of PIGT and its altered variants in PNH and other disorders.

The PubMed catalog of articles on PNH also includes studies on the white blood cells and other cells involved in the hemolytic anemia seen in PNH. These articles provide valuable information on the pathogenesis of PNH and the role of these cells in the disease.

This compilation of scientific articles on PubMed offers a wealth of information for researchers, clinicians, and patients interested in PNH. References to more articles, genetic testing resources, and OMIM entries are available to further explore the topic.

References