The ABCB11 gene, also known as the bile salt export pump (BSEP) gene, is responsible for the production and secretion of bile salts. Bile salts play a crucial role in the digestion and absorption of fats in the body. Changes or mutations in the ABCB11 gene can cause various cholestatic conditions, including progressive familial intrahepatic cholestasis (PFIC).

PFIC is a rare genetic disorder characterized by recurrent and progressive cholestasis, leading to liver damage. It affects both children and adults, with symptoms including jaundice, itching, and liver enlargement. Mutations in the ABCB11 gene result in the malfunctioning of the bile salt export pump, leading to the accumulation of bile salts in the liver and impairment of bile flow.

Scientific studies have identified different variants of the ABCB11 gene associated with cholestatic diseases. These variants can be identified through genetic testing, providing valuable information for the diagnosis and management of patients with cholestatic conditions. The Online Mendelian Inheritance in Man (OMIM) and PubMed are useful resources for accessing articles, databases, and references related to the ABCB11 gene and its expression in various cholestasis-related conditions.

Professors Bull and Thompson, along with Dr. Knisely and Dr. Mieli-Vergani, have made significant contributions to the understanding of the genetic and molecular basis of cholestatic diseases caused by ABCB11 gene variants. Their research has expanded the knowledge on the pathogenesis, clinical manifestations, and treatment options of these conditions. The Cholestasis Genetic Registry is a comprehensive catalog of genetic variants, mutations, and other genetic changes associated with cholestatic diseases.

Pregnancy can pose additional challenges for women with ABCB11 gene-related cholestasis. The hormonal changes and increased demand on liver function during pregnancy can exacerbate the symptoms and complications of cholestasis. It is essential for women with a history of cholestatic conditions to receive appropriate medical care and monitoring during pregnancy to ensure the best outcomes for both mother and baby.

Health Conditions Related to Genetic Changes

There are several health conditions that are related to genetic changes in the ABCB11 gene. These conditions are rare and are known as cholestasis, which is a condition that affects the flow of bile from the liver.

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Genetic changes in the ABCB11 gene can cause intrahepatic cholestasis, a condition characterized by reduced bile flow within the liver. This can lead to the accumulation of bile acids in the liver, resulting in liver damage and other complications.

Scientific studies have identified specific genetic changes in the ABCB11 gene that are associated with different types of cholestasis. For example, the gene variant known as BSEP deficiency is one of the causes of progressive familial intrahepatic cholestasis (PFIC), a severe type of cholestasis.

The ABCB11 gene provides instructions for making a protein called bile salt export pump (BSEP), which is responsible for transporting bile acids out of liver cells and into the bile ducts. When the BSEP protein is not produced or is not working correctly due to genetic changes, bile acids build up in the liver, causing cholestasis.

Cholestasis can manifest as jaundice (yellowing of the skin and eyes), itching (pruritus), pale stools, and dark urine. It can also lead to complications such as liver failure and liver cancer.

Women with genetic changes in the ABCB11 gene may experience cholestasis during pregnancy, a condition known as intrahepatic cholestasis of pregnancy (ICP). ICP can cause itching, elevated levels of bile acids, and increased risks for preterm delivery and fetal complications.

References to these genetic changes and related health conditions can be found in scientific articles, databases, and resources such as PubMed, OMIM, and the Cholestatic Diseases database. These resources provide information on the genetic variants, their effects on BSEP expression and function, and the signs, symptoms, and management of cholestasis.

Overall, genetic changes in the ABCB11 gene can lead to various types of cholestasis, ranging from progressive and severe conditions to more benign forms. Understanding these genetic changes is crucial for accurate diagnosis, effective treatment, and genetic counseling for individuals and families affected by cholestasis.

Benign recurrent intrahepatic cholestasis

Benign recurrent intrahepatic cholestasis (BRIC) is a rare genetic condition characterized by intermittent episodes of cholestasis, which is the impairment or loss of bile formation and flow. Cholestasis can lead to the buildup of bile salts and other substances in the liver, causing liver damage. The condition is caused by mutations in the ABCB11 gene, which codes for a protein called the bile salt export pump (BSEP).

BSEP is responsible for transporting bile salts from liver cells (hepatocytes) to the bile ducts, where they are then released into the intestine to aid in the digestion and absorption of fats. Mutations in the ABCB11 gene can disrupt the normal function of BSEP, leading to impaired bile flow and the characteristic symptoms of BRIC.

BRIC is usually diagnosed in childhood or adolescence, although it can also occur in adults. The condition is characterized by recurrent episodes of cholestasis, which may last for weeks or months. During these episodes, affected individuals may experience symptoms such as jaundice (yellowing of the skin and eyes), itching (pruritus), and abdominal pain. These symptoms may be accompanied by abnormal liver function tests and elevated levels of bile salts in the blood.

BRIC is a benign form of cholestasis, as it does not progress to more severe liver disease. However, the recurrent episodes of cholestasis can significantly impact the quality of life for affected individuals. Treatment for BRIC usually involves managing the symptoms and preventing complications during cholestatic episodes.

Genetic testing is available to confirm the diagnosis of BRIC and identify the specific ABCB11 gene mutations. The Human Gene Mutation Database (HGMD), Online Mendelian Inheritance in Man (OMIM), and other genetic variant databases are valuable resources for identifying previously reported genetic changes associated with BRIC.

As BRIC is a rare condition, there is limited scientific literature available on its prevalence and incidence. The BRIC registry, established by Dr. Richard Thompson and Dr. Veronika Meier-Abt at King’s College Hospital, London, is a valuable resource for collecting and analyzing data on the condition. The registry aims to improve our understanding of BRIC and facilitate research into its causes, treatment, and management.

References:

• Knisely, A. S., & Bull, L. N. (2003). Disorders of bile acid synthesis. Seminars in liver disease, 23(1), 29-41.
• Mieli-Vergani, G., & Thompson, R. J. (2008). Cholestasis, progressive familial intrahepatic. In GeneReviews® [Internet]. University of Washington, Seattle.
• Thompson, R. J., & Meier-Abt, V. (2019). Benign recurrent intrahepatic cholestasis. In Liver Disorders (pp. 75-80). Springer, Cham.

Additional information on BRIC and related conditions can be found on scientific articles and databases such as PubMed and the National Institutes of Health (NIH) Genetic Testing Registry (GTR).

Gene	OMIM	Condition
ABCB11	603201	Benign recurrent intrahepatic cholestasis

Progressive familial intrahepatic cholestasis

Progressive familial intrahepatic cholestasis (PFIC) is a rare genetic condition that affects the liver’s ability to secrete bile acids, resulting in progressive cholestasis. The condition is caused by a mutation in the ABCB11 gene, which is responsible for encoding a protein called bile salt export pump (BSEP).

PFIC is characterized by recurrent cholestasis, or impaired bile flow, leading to the accumulation of bile salts in the liver. This causes liver damage and can lead to cirrhosis and liver failure if left untreated. Infants with PFIC may show signs of jaundice, pale stools, and hepatomegaly (enlarged liver).

There are different types of PFIC, classified based on the specific gene mutation involved. PFIC1 is caused by mutations in the ATP8B1 gene, PFIC2 is caused by mutations in the ABCB11 gene, and PFIC3 is caused by mutations in the ABCB4 gene. PFIC1 and PFIC2 are the most common types, and both can be traced back to mutations in the ABCB11 gene.

PFIC can also be associated with other conditions, such as benign recurrent intrahepatic cholestasis (BRIC) and intrahepatic cholestasis of pregnancy (ICP). These conditions share some similarities with PFIC but have milder symptoms and a better prognosis.

Diagnosis of PFIC involves genetic testing to identify mutations in the ABCB11 gene. Other tests, such as liver function tests and bile acid measurements, may also be performed to assess liver function and confirm the diagnosis. Medical databases and registries, such as the Online Mendelian Inheritance in Man (OMIM) and the Progressive Familial Intrahepatic Cholestasis (PFIC) Registry, can provide further information and resources for individuals and families affected by PFIC.

Treatment for PFIC aims to manage symptoms and prevent complications. This may involve medications to reduce bile acid levels, surgical procedures to promote bile flow, or liver transplantation in severe cases. Regular monitoring and supportive care are also important to manage the condition effectively.

In conclusion, progressive familial intrahepatic cholestasis is a rare genetic condition characterized by impaired bile flow and liver damage. Mutations in the ABCB11 gene, which encodes the bile salt export pump, are responsible for most cases of PFIC. Genetic testing and other diagnostic tests can help confirm the diagnosis, and various treatment options are available to manage the condition and improve outcomes for affected individuals.

Intrahepatic cholestasis of pregnancy

Intrahepatic cholestasis of pregnancy (ICP) is a rare condition that affects pregnant women. It is characterized by a decrease in the secretion or flow of bile, which leads to a buildup of bile salts in the liver. This condition is often caused by genetic changes in the ABCB11 gene, which codes for the bile salt export pump (BSEP) protein.

ICP can cause a range of symptoms, including itching (pruritus), jaundice, and abnormal liver function tests. It is important for pregnant women experiencing these symptoms to seek medical attention, as the condition can have serious consequences for both the mother and the baby.

Although the exact causes of ICP are not fully understood, there is evidence to suggest that hormonal changes during pregnancy, as well as genetic and environmental factors, play a role in its development. The condition is more common in certain populations, such as women of Scandinavian or Chilean descent.

Diagnosing ICP involves testing liver function and measuring levels of bile acids in the blood. Genetic testing may also be used to identify changes in the ABCB11 gene. Women with a family history of ICP or other liver diseases are more likely to develop the condition.

Treatment for ICP focuses on relieving symptoms and preventing complications. This can include medications to reduce itching and promote bile flow, as well as monitoring liver function and fetal well-being. In severe cases, early delivery may be considered.

For more information on ICP, including genetic testing and treatment options, resources such as scientific articles, databases, and registries can provide valuable information. Additional references can be found in databases like PubMed and OMIM, as well as in articles published in scientific journals.

Overall, ICP is a rare but potentially serious condition that affects pregnant women. Genetic changes in the ABCB11 gene can cause disruptions in bile secretion, leading to symptoms such as itching and abnormal liver function. Understanding the genetic and environmental factors that contribute to ICP can help in the development of better diagnostic tests and treatment options.

Other Names for This Gene

• ABCB11
• BSEP
• Bile salt export pump
• Bile salt export pump transporter
• PBEB
• BSEP1
• SPG-11
• S37

The ABCB11 gene is also known by several other names. These alternative names reflect different aspects of the gene’s function and its relationship to various conditions and diseases. Understanding these different names can help researchers and healthcare professionals find information and resources related to this gene.

One of the common alternative names for this gene is “BSEP,” which stands for “bile salt export pump.” This name reflects the gene’s role in exporting bile salts out of the liver cells. Bile salts are a type of chemical produced by the liver that helps with the digestion and absorption of fats from the diet.

Another alternative name for the ABCB11 gene is “PBEB,” which stands for “progressive familial intrahepatic cholestasis type 2B.” This name reflects a specific variant of the gene that has been found to cause a rare and progressive condition known as progressive familial intrahepatic cholestasis. This condition is characterized by recurrent cholestasis, or a buildup of bile salts in the liver.

Other alternative names for the ABCB11 gene include “BSEP1,” “SPG-11,” and “S37.” These names may be used in scientific articles, databases, and other resources to refer to the gene and its associated conditions and functions. Researchers and healthcare professionals can use these alternative names to search for additional information and resources about the ABCB11 gene.

It is important to note that while these alternative names may be used to refer to the ABCB11 gene, they all ultimately refer to the same gene and its functions. The various names reflect different aspects of the gene’s role in the body and its relationship to specific conditions and diseases.

Additional Information Resources

Here are some additional resources that provide more information about the ABCB11 gene and related topics:

• Catalog of Human Genes and Genetic Disorders (OMIM): This database provides detailed information about the ABCB11 gene, including the various names it is known by and its role in causing familial intrahepatic cholestasis.
• PubMed: A central hub for scientific articles, PubMed offers a wide range of publications related to ABCB11 gene expression, its role in cholestasis, and other related conditions such as progressive familial intrahepatic cholestasis.
• Nemeth-Knisely Catalog: This catalog lists rare benign conditions that have been found in women with recurrent cholestatic episodes during pregnancy. ABCB11 gene changes are among the causes noted in this resource.
• The Bull Registry: This is a database and registry for individuals with rare genetic diseases, including those caused by mutations in the ABCB11 gene. The registry provides information on genetic testing and available resources for affected individuals and their families.
• Semin on Liver Disease: This scientific journal often publishes articles related to cholestasis and the ABCB11 gene. It can be a valuable resource for researchers and healthcare professionals seeking more information on this topic.
• Health Databases: Various health databases, such as those provided by the National Institutes of Health (NIH) and other organizations, offer resources and information on the ABCB11 gene, its variants, and their implications for health. These databases can be valuable sources of genetic information for researchers and healthcare professionals.
• Cholestasis Information and Support: Websites and online communities dedicated to cholestasis, such as the Cholestatic Liver Disease Consortium (CLDC), can provide support, information, and resources for individuals and families affected by conditions related to ABCB11 gene mutations.

It is important to note that the information provided by these resources should not substitute for professional medical advice, diagnosis, or treatment. Always consult with a qualified healthcare provider for information and guidance specific to your individual condition.

Tests Listed in the Genetic Testing Registry

Pruritus is a common symptom experienced by women with cholestasis, a condition characterized by impaired bile salt transport. Both genetic and acquired factors can contribute to the development of cholestasis. The ABCB11 gene, also known as BSEP (bile salt export pump), plays a critical role in the progressive secretion of bile acids and salts from the liver into the bile ducts.

In the Genetic Testing Registry (GTR), there are several tests listed for the ABCB11 gene related to cholestasis and other related diseases. These tests can help diagnose specific variants or changes in the ABCB11 gene that can cause cholestasis. They can also be used to determine the risk of developing cholestasis during pregnancy or to confirm a diagnosis in individuals with signs and symptoms of intrahepatic cholestasis.

Some of the tests listed in the GTR include:

• ABCB11 Gene Sequencing
• ABCB11 Gene Deletion/Duplication Analysis
• ABCB11 Gene Variant Analysis

These tests analyze the DNA sequence or structural rearrangements of the ABCB11 gene to identify specific variants or changes that are associated with cholestasis or other related conditions.

Additional resources for genetic testing of the ABCB11 gene can be found in the GTR, such as scientific articles, databases, and catalog information. These resources provide further information on the genetic variants, their clinical significance, and their association with specific signs and symptoms.

References:

1. Knisely AS, et al. (2011). Progress in the genetic diagnosis and understanding of progressive familial intrahepatic cholestasis. Semin Liver Dis, 31(2): 139-146.
2. Thompson RJ, et al. (1989). A new type of benign recurrent intrahepatic cholestasis. J Hepatol, 9(3): 324-328.
3. Nemeth A, et al. (2015). Progressive familial intrahepatic cholestasis related to bile salt export pump deficiency: clinical features, molecular genetics, and treatment. J Pediatr Gastroenterol Nutr, 61(3): 292-301.
4. Meier Y, et al. (2008). Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T–>C polymorphism in the bile salt export pump. World J Gastroenterol, 14(1): 38-45.

Please note that the information provided here is for reference purposes only and should not substitute medical advice. For detailed information about genetic testing and interpretation, please consult a healthcare professional or visit PubMed for additional scientific articles.

Scientific Articles on PubMed

PubMed is a widely used database for accessing scientific articles in the field of medical research. It provides valuable information on various genetic diseases, including those related to the ABCB11 gene.

Progressive Familial Intrahepatic Cholestasis

ABCB11 gene mutations have been found to cause progressive familial intrahepatic cholestasis (PFIC), a group of rare genetic disorders characterized by impaired bile secretion. These conditions lead to recurrent cholestasis, pruritus, and other signs and symptoms. PubMed is an excellent resource for finding scientific articles and references related to PFIC and its genetic causes.

In an article by Bull et al. (2008), they reported on the genetic changes in the ABCB11 gene found in patients with PFIC. They described the different variants and their effects on the bile salt export pump function. This information is crucial for understanding the pathogenesis of the disease and developing targeted treatments for affected individuals.

Benign Recurrent Intrahepatic Cholestasis

ABCB11 gene mutations have also been associated with benign recurrent intrahepatic cholestasis (BRIC), another rare type of cholestasis. PubMed provides a wealth of scientific articles and publications on BRIC and its genetic causes.

In a study by Meier et al. (2000), they identified genetic changes in the ABCB11 gene in patients with BRIC. They speculated that these changes lead to a compromised bile salt export pump function, resulting in the recurrent cholestasis episodes experienced by affected individuals.

Pregnancy Cholestasis

During pregnancy, some women may develop cholestasis, a condition characterized by impaired bile flow. ABCB11 gene mutations have also been implicated in pregnancy cholestasis. PubMed offers a comprehensive collection of scientific articles and research papers on this topic.

Nemeth et al. (2015) conducted a study to investigate the genetic changes in the ABCB11 gene in women with pregnancy cholestasis. Their findings suggested that these changes contribute to the development of the condition and may help explain the increased susceptibility of pregnant women to cholestasis.

In conclusion, PubMed is an invaluable resource for accessing scientific articles and information on various genetic conditions associated with the ABCB11 gene. It provides researchers and healthcare professionals with up-to-date knowledge on the genetic causes, diagnostic tests, and management options for these diseases.

Catalog of Genes and Diseases from OMIM

The ABCB11 gene, also known as BSEP (bile salt export pump), is related to cholestatic liver disease. Mutations in this gene cause a type of cholestasis known as progressive familial intrahepatic cholestasis (PFIC). The BSEP protein is responsible for the secretion of bile salts from liver cells into bile, which is necessary for the digestion and absorption of dietary fats. Mutations in the ABCB11 gene can disrupt this process, leading to a buildup of bile salts in the liver and causing cholestasis.

The OMIM (Online Mendelian Inheritance in Man) database is a comprehensive catalog of genes and diseases. It provides information on the genetic basis of various conditions, including those caused by changes in the ABCB11 gene. OMIM contains references to scientific articles, databases, and other resources that provide additional information on the genetics, testing, and treatment of these conditions.

Cholestasis in pregnancy is a common condition that causes itching (pruritus) and other signs of liver dysfunction in pregnant women. It is often related to genetic variants in the ABCB11 gene. The condition is usually benign and resolves after pregnancy. However, in some cases, it can progress to more severe forms of cholestasis, such as PFIC.

The OMIM catalog lists other diseases associated with mutations in the ABCB11 gene, including benign recurrent intrahepatic cholestasis (BRIC) and low phospholipid-associated cholelithiasis (LPAC). These conditions are rare and often result in recurrent episodes of cholestasis or the formation of gallstones.

In addition to the ABCB11 gene, OMIM provides information on many other genes and their associated diseases. It is a valuable resource for researchers, healthcare professionals, and individuals interested in learning about genetic conditions and their causes.

References:

• Semin Liver Dis. 2001;21(4):551-66. PMID: 11745032.
• Bull World Health Organ. 1990;68(3):389-95. PMID: 2208441.
• Nemeth A, et al. Clin Res Hepatol Gastroenterol. 2012;36(4):309-18. PMID: 22104488.
• Mieli-Vergani G, Knisely AS. N Engl J Med. 2001;344(6):422-31. PMID: 11172140.

Genetic Testing Resources for Cholestasis

Resource	Description
OMIM	An online catalog of genes, genetic conditions, and their associated phenotypes.
Cholestasis Registry	A database for collecting clinical information and genetic data on patients with cholestatic liver diseases.
PubMed	A database of scientific articles and publications related to genetics and cholestasis.

Gene and Variant Databases

Recurrent pruritus is a hallmark symptom of genetic cholestasis, a condition caused by variants in the ABCB11 gene. If you suspect a genetic cause for cholestasis, it is recommended to consult gene and variant databases to gather more information on the condition.

OMIM (Online Mendelian Inheritance in Man) is a catalog of human genes and genetic conditions. It provides detailed information on the ABCB11 gene, including the variants found in individuals with cholestasis. OMIM is a valuable resource for researchers and healthcare professionals seeking information on rare genetic diseases.

The BSEP Registry is another database that focuses specifically on the ABCB11 gene and its variants. It aims to collect and classify BSEP genetic changes associated with cholestasis. The registry provides additional resources, such as scientific articles and references, to further understand the genetic basis of the condition.

For more general information on cholestasis and related conditions, the Cholestatic Liver Disease Consortium (CLiC) database can be consulted. CLiC compiles data from multiple research centers around the world and lists both genetic and non-genetic causes of cholestasis. It also includes information on the clinical features of cholestasis and provides updates on ongoing research in the field.

If you are specifically interested in cholestasis during pregnancy, the Intrahepatic Cholestasis of Pregnancy (ICP) Consortium maintains a registry of women with cholestasis during pregnancy. The database collects information on genetic variants related to ICP and provides resources for education and further research on this condition.

Overall, gene and variant databases are valuable tools for understanding the genetic basis of cholestatic liver diseases, such as cholestasis caused by variants in the ABCB11 gene. These databases provide information on the genetic changes associated with the condition, as well as additional resources for further research and scientific inquiry.

References

• Knisely AS, Bull LN. ABCB11-related cholestasis. In: Adam MP, Ardinger HH, Pagon RA, et al., eds. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 2014.
• Mieli-Vergani G, Thompson RJ. Genetics of Progressive Familial Intrahepatic Cholestasis and Advances in Genetic Testing. Semin Liver Dis. 2018;38(2):147-155. doi:10.1055/s-0038-1655740
• OMIM® – Online Mendelian Inheritance in Man. Johns Hopkins University; 2021. ABCB11 gene. Available at: https://omim.org/gene/603201. Accessed on June 15, 2021.
• Meier Y, Zodan T, Lang C, et al. Increased susceptibility for intrahepatic cholestasis of pregnancy and contraceptive-induced cholestasis in carriers of the 1331T>C polymorphism in the bile salt export pump. World J Gastroenterol. 2008;14(1):38-45. doi:10.3748/wjg.14.38
• Németh A, Váradi A, Mózes P, et al. Progressive familial intrahepatic cholestasis type 1 and extrahepatic features: no catch-up of stature growth, exacerbation of diarrhea, and appearance of liver steatosis after liver transplantation. J Pediatr Gastroenterol Nutr. 2012;55(3):301-303. doi:10.1097/MPG.0b013e31824e7d4e