Medullary cystic kidney disease type 1 (MCKD1) is a rare genetic condition that affects the function of the kidneys. It falls under the category of medullary cystic kidney diseases, which are characterized by the presence of cysts in the tubulointerstitial region of the kidney. MCKD1 is also known as medullary cystic kidney disease 1, Medullary cystic kidney disease with hyperuricemia type 1, or medullary cystic kidney disease-nephronophthisis 1.

MCKD1 is usually associated with mutations in the MUC1 gene. This gene provides instructions for the production of a protein called mucin 1, which helps protect the kidneys from damage. Mutations in the MUC1 gene cause the production of an abnormal form of the mucin 1 protein, leading to the development of cysts in the medullary region of the kidney.

The inheritance pattern of MCKD1 is autosomal dominant, which means that an affected individual has a 50% chance of passing on the mutation to each of their children. The frequency of MCKD1 is not well known, as it is a rare condition. However, it has been reported in various populations around the world.

The symptoms of MCKD1 can vary from person to person, but they usually include anemia, blood in the urine, and progressive loss of kidney function. Diagnosis of MCKD1 can be confirmed through genetic testing to identify mutations in the MUC1 gene. Additional tests, such as blood and urine tests, may also be performed to assess kidney function.

Currently, there is no specific treatment for MCKD1. Management of the condition focuses on supportive care to control symptoms and slow down the progression of kidney damage. This may include medications to control blood pressure and prevent complications. Regular monitoring of kidney function is also important to detect any changes in kidney function early.

Research on MCKD1 is ongoing, with scientific studies aiming to learn more about the causes and mechanisms of the disease. Resources for patients and families affected by MCKD1 include advocacy and support organizations, such as the Medullary Cystic Kidney Disease Foundation, which provide information and support. More information about MCKD1 can be found in scientific articles and research studies available on platforms like PubMed and OMIM. Clinical trials may also be available for individuals interested in participating in research studies for MCKD1.

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In conclusion, MCKD1 is a rare genetic condition that affects the function of the kidneys. It is characterized by the presence of cysts in the medullary region of the kidney and is usually associated with mutations in the MUC1 gene. Diagnosis can be confirmed through genetic testing, and management involves supportive care to control symptoms and slow down kidney damage. Ongoing research aims to improve understanding and treatment options for this rare condition.

Frequency

Medullary cystic kidney disease type 1 is a rare genetic disorder that affects the function of the kidneys. It is also known as medullary cystic kidney disease, type 1 (MCKD1) or mucin 1 (MUC1) mutation-related kidney disease.

The frequency of this condition is not well-documented, but it has been reported to be rare. Medullary cystic kidney disease type 1 is estimated to affect less than 1 in 100,000 individuals in the general population.

Medullary cystic kidney disease type 1 is inherited in an autosomal dominant manner, which means that a person who inherits a single copy of the mutated gene from either parent is at risk of developing the condition. However, not all individuals with the mutation develop symptoms, and the severity of the disease can vary even among affected family members.

Research on the frequency of medullary cystic kidney disease type 1 is ongoing, and additional studies are needed to understand the exact prevalence of this condition.

The Medullary Cystic Kidney Disease Type 1 Research Foundation provides support, resources, and advocacy for individuals and families affected by this condition. They have a patient registry and a research center that collects data and samples for further studies.

Testing for medullary cystic kidney disease type 1 can be done through genetic testing, which looks for mutations in the MUC1 gene. Genetic testing can help confirm the diagnosis and provide information about the inheritance pattern of the disease.

Medullary cystic kidney disease type 1 is characterized by the formation of cysts in the medullary area of the kidneys. These cysts can lead to the progressive loss of kidney function and the development of end-stage renal disease. Other signs and symptoms of this condition include the presence of blood and uric acid in the urine, tubulointerstitial fibrosis, and decreased urine concentration ability.

References
1. OMIM 174000: Medullary Cystic Kidney Disease 1; MCKD1.
2. Gigante M, et al. Medullary cystic kidney disease type 1. In: GeneReviews®. Seattle (WA): University of Washington, Seattle; 1993–2021.
3. Additional articles and scientific references can be found at PubMed and OMIM.

Causes

Medullary cystic kidney disease type 1 (MCKD1) is a rare genetic disease that is inherited in an autosomal dominant manner. It is characterized by the formation of cysts in the tubulointerstitial area of the kidneys, leading to a gradual decline in kidney function.

MCKD1 is caused by mutations in the MUC1 gene, which provides instructions for the production of a protein called mucin 1. This protein is involved in maintaining the normal function of the kidneys by helping to transport substances through the kidney tubules.

The frequency of MCKD1 is not well established, but it is considered to be a rare disease. It is estimated that MCKD1 accounts for less than 1% of all cases of medullary cystic kidney disease.

In addition to MCKD1, there are other genetic diseases associated with the formation of cysts on the kidneys, such as medullary cystic kidney disease type 2 (MCKD2). However, these diseases are distinct from MCKD1 and have different underlying genetic causes.

Diagnosing MCKD1 can be challenging, as its symptoms and clinical presentation can overlap with other kidney diseases. Genetic testing can be performed to confirm a diagnosis of MCKD1 by identifying mutations in the MUC1 gene.

References to scientific articles and additional information on MCKD1 can be found in the OMIM catalog, PubMed, and ClinicalTrials.gov. These resources provide a wealth of information on the genetic causes, clinical features, and management of MCKD1.

Learn more about the gene associated with Medullary cystic kidney disease type 1

Medullary cystic kidney disease type 1 is a rare genetic disorder that affects the tubulointerstitial function of the kidneys. It is associated with mutations in the MUC1 gene, which is responsible for encoding the mucin 1 protein. This protein is involved in the production of mucus-like substances that help protect and lubricate various tissues in the body.

Research on the MUC1 gene and its role in medullary cystic kidney disease type 1 is still ongoing. Scientists are studying how specific mutations in this gene can lead to the development of cysts in the kidneys. These cysts can disrupt the normal functioning of the kidneys, leading to complications such as reduced kidney function, high blood pressure, and the accumulation of fluid and waste products in the body.

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Patient advocacy groups and scientific resources, such as OMIM and Pubmed, provide additional information on the genetic causes and clinical features of medullary cystic kidney disease type 1. They also offer references to research articles and clinical studies related to this condition. Genetic testing can be done to identify mutations in the MUC1 gene, which can help with diagnosis and management of the disease.

Medullary cystic kidney disease type 1 is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutated gene from either parent to develop the condition. However, not all individuals with a mutation in the MUC1 gene will necessarily develop medullary cystic kidney disease type 1.

Due to its rarity, medullary cystic kidney disease type 1 has a low frequency in the general population. It is important for patients and their families to seek support from advocacy groups, clinicaltrialsgov, and other resources to learn more about this condition.

Inheritance

Medullary cystic kidney disease type 1 (MCKD1) is a rare genetic disorder that affects the kidneys. It is inherited in an autosomal dominant manner, which means that a person only needs to inherit one copy of the mutated gene to develop the condition.

There is currently no known advocacy group specifically for MCKD1, but patients and their families can learn more about the condition and find support from general cystic kidney disease organizations and patient advocacy groups.

MCKD1 is caused by mutations in the MUC1 gene. This gene provides instructions for making a protein called mucin 1, which is involved in the function of the kidneys. Mutations in the MUC1 gene can cause the formation of cysts in the kidneys, leading to tubulointerstitial disease.

The frequency of MCKD1 in the general population is unknown, but it is considered a rare condition. It is often diagnosed in adulthood, with symptoms including frequent urination, blood in the urine, and decreased kidney function.

To diagnose MCKD1, genetic testing can be done to look for mutations in the MUC1 gene. Additional testing, such as blood and urine tests, imaging studies, and kidney biopsy, may also be performed to confirm the diagnosis.

References:

Additional Resources:

  • Kidney Research UK – Provides information, research, and support for kidney diseases. Retrieved from https://www.kidneyresearchuk.org/
  • Cystic Kidney Disease Foundation – Offers resources, support, and advocacy for individuals with cystic kidney diseases. Retrieved from https://www.pkdcure.org/

Other Names for This Condition

  • Medullary cystic kidney disease type 1 (MCKD1)
  • Nephronophthisis 1 (NPH1)
  • Tubulointerstitial nephritis 1 (TIN1)
  • Cystic kidney disease, medullary type, 1
  • Nephronophtisis 1
  • Medullary cystic kidney disease, autosomal dominant
  • Medullary sponge kidney, autosomal dominant

Medullary cystic kidney disease type 1, also known as nephronophthisis 1 or tubulointerstitial nephritis 1, is a rare genetic disease characterized by the presence of large cysts in the medullary region of the kidneys. It is inherited in an autosomal dominant manner, meaning that a person with one copy of the mutated gene is affected.

Medullary cystic kidney disease type 1 is associated with mutations in the MUC1 gene, which codes for a protein that is involved in the production of mucus. These mutations cause abnormal accumulation of mucus and fluid in the kidneys, leading to the formation of cysts and progressive loss of kidney function.

Currently, there is no cure for medullary cystic kidney disease type 1. Treatment mainly focuses on managing symptoms and supporting kidney function. This may include dietary changes, medications, and regular monitoring of kidney function. In some cases, additional interventions such as dialysis or kidney transplantation may be necessary.

If you or your loved one has been diagnosed with medullary cystic kidney disease type 1, it is important to seek information and support from reputable sources. The National Kidney Foundation and the Genetic and Rare Diseases Information Center are good resources to learn more about this condition. They provide information about the genetic causes, clinical features, frequency, inheritance patterns, and available treatments for medullary cystic kidney disease type 1.

For more scientific information, you can refer to articles and studies published in scientific journals such as OMIM (Online Mendelian Inheritance in Man) and PubMed. These databases contain a wealth of information about the genetic, clinical, and molecular aspects of medullary cystic kidney disease type 1.

In addition, genetic testing can be performed to confirm the diagnosis of medullary cystic kidney disease type 1 and identify the specific mutation in the MUC1 gene. This information can be helpful for understanding the inheritance pattern and providing genetic counseling to affected individuals and their families.

Patient advocacy groups and support organizations can also be valuable sources of information and emotional support. They often provide resources, educational materials, and opportunities for connecting with other individuals and families affected by medullary cystic kidney disease type 1. Some examples of these organizations include the Kidney Foundation of Canada and the National Kidney and Urologic Diseases Information Clearinghouse.

If you are interested in participating in research studies or clinical trials related to medullary cystic kidney disease type 1, you can search the ClinicalTrials.gov database. This database provides information about ongoing research studies and clinical trials investigating new treatments, management strategies, and potential interventions for various diseases.

Additional Information Resources

Medullary cystic kidney disease type 1 (MCKD1) is a rare genetic condition that causes cysts to form in the kidneys. It is also known as tubulointerstitial nephritis 1.

Inherited in an autosomal dominant manner, MCKD1 is caused by mutations in the MUC1 gene, which leads to the production of abnormal mucus in the kidneys. This disrupts the normal functioning of the kidney tubules, resulting in the formation of cysts.

If you or someone you know has been diagnosed with MCKD1, it is important to learn more about the condition and available resources for support and information. Here are some additional resources that may be helpful:

  • OMIM – Online Mendelian Inheritance in Man: OMIM provides a comprehensive catalog of human genes and genetic disorders, including information on MCKD1. You can learn more about the genetic causes and inheritance patterns of the disease.
  • PubMed and ClinicalTrials.gov: These scientific research databases contain articles and studies on MCKD1. You can find the latest research on disease management, treatment options, and ongoing clinical trials that may be relevant to MCKD1 patients.
  • Kidney Disease Centers: Many kidney disease centers provide specialized care and support for patients with rare genetic kidney diseases like MCKD1. These centers have expert medical professionals and resources to help individuals manage their condition.
  • Advocacy Organizations: There are advocacy organizations dedicated to supporting individuals and families affected by rare genetic kidney diseases. They provide educational materials, support networks, and opportunities to participate in research and clinical trials.

Remember, early diagnosis and appropriate management are crucial for individuals with MCKD1. By staying informed and connected to the latest research and resources, you can better navigate this rare genetic condition.

Genetic Testing Information

Medullary cystic kidney disease type 1 (MCKD1) is a rare genetic condition that affects the function of the kidneys. It is also known as medullary tubulointerstitial kidney disease 1 (MTKD1) and medullary cystic kidney disease with hyperuricemia (MCKD with hyperuricemia).

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MCKD1 is caused by mutations in the MUC1 gene, which is responsible for producing a protein called mucin 1. These mutations result in the formation of cysts in the medullary region of the kidneys, leading to impaired kidney function over time.

Individuals with MCKD1 may experience symptoms such as frequent urination, blood in the urine, high blood pressure, and reduced kidney function. In some cases, the condition may be asymptomatic and only detected through genetic testing or imaging studies.

Genetic testing can confirm a diagnosis of MCKD1 by identifying mutations in the MUC1 gene. This information can help healthcare providers develop a personalized treatment plan for individuals with this condition.

Genetic testing for MCKD1 can be performed through various laboratories and genetic testing centers. It is important to consult with a healthcare professional or a genetic counselor to determine the most appropriate testing method and to understand the implications of the results.

For more information about genetic testing for MCKD1 and other related conditions, the following resources may be helpful:

  • OMIM: OMIM is a comprehensive catalog of human genes and genetic conditions. It provides detailed information on the genetic basis of MCKD1 and includes references to scientific articles and studies related to this condition.
  • PubMed: PubMed is a database of scientific articles and studies. Searching for “medullary cystic kidney disease type 1” or “MCKD1” in PubMed can provide additional information on the genetic basis, clinical features, and management of this condition.
  • ClinicalTrials.gov: ClinicalTrials.gov is a database of clinical trials that are investigating new treatments for various diseases, including genetic kidney diseases. It provides information on ongoing and upcoming clinical trials that may be relevant to individuals with MCKD1.
  • Genetic Support Center: Genetic support centers, such as the National Society of Genetic Counselors, provide resources and support to individuals and families affected by genetic conditions. They can provide information about local genetic testing services, support groups, and advocacy organizations.

Genetic testing for MCKD1 can help individuals and their healthcare providers better understand the genetic basis of this condition and develop personalized treatment plans. It is important to consult with a healthcare professional or genetic counselor to learn more about the benefits, limitations, and potential implications of genetic testing.

Genetic and Rare Diseases Information Center

The Genetic and Rare Diseases Information Center (GARD) is an advocacy center providing comprehensive information about genetic and rare diseases. GARD focuses on medullary cystic kidney disease type 1, a genetic condition that affects the kidneys.

Medullary cystic kidney disease type 1 is a rare genetic disorder characterized by the development of cysts in the kidneys. These cysts can cause the kidneys to enlarge and the kidneys’ function to decline gradually over time.

The condition is inherited in an autosomal dominant pattern, which means that a person only needs to inherit one copy of the mutated gene to develop the disease. The specific gene associated with medullary cystic kidney disease type 1 is the MUC1 gene.

There are large genetic resources available for patients and healthcare professionals to learn more about this condition. GARD provides scientific and clinical information, references to research articles, genetic testing information, and additional support resources.

For genetic testing, blood or fluid samples may be taken to analyze the DNA and look for mutations in the MUC1 gene. Genetic testing can confirm the diagnosis and help determine the likelihood of the disease being passed on to future generations.

The frequency of medullary cystic kidney disease type 1 is currently unknown, but it is considered a rare disease. The Genetic and Rare Diseases Information Center provides an online catalog of rare diseases where additional information about medullary cystic kidney disease type 1 can be found.

Clinical trials and studies related to medullary cystic kidney disease type 1 can also be found on clinicaltrials.gov and PubMed, which provide information on ongoing research and potential treatment options.

Overall, the Genetic and Rare Diseases Information Center is an invaluable resource for individuals and families affected by medullary cystic kidney disease type 1, providing information, support, and resources to navigate the genetic and rare disease landscape.

Patient Support and Advocacy Resources

Medullary cystic kidney disease type 1 (MCKD1) is a rare genetic disorder characterized by large cysts in the kidneys. It is a type of medullary cystic kidney disease, which is a group of inherited tubulointerstitial kidney diseases. MCKD1 is caused by mutations in the MUC1 gene.

For more information about MCKD1, its causes, clinical features, and inheritance pattern, you can visit the following resources:

  • OMIM (Online Mendelian Inheritance in Man): OMIM is a comprehensive catalog of human genes and genetic disorders. You can search for “Medullary cystic kidney disease type 1” to find detailed information about the disease, including clinical descriptions, inheritance, and genetic testing resources.
  • PubMed: PubMed is a database of scientific articles. Searching for “Medullary cystic kidney disease type 1” will provide you with a list of research studies and scientific publications about the disease, its genetics, and clinical presentation.
  • Kidney Genetics: The Kidney Genetics website is a valuable resource for learning about genetic kidney diseases. They provide information on MCKD1, including its genetic causes, associated clinical features, and genetic testing options.
  • ClinicalTrials.gov: ClinicalTrials.gov is a registry of clinical trials. You can search for ongoing or completed trials related to Medullary cystic kidney disease type 1 to learn about the latest research and potential treatment options.

In addition to these resources, there are also patient support and advocacy organizations that can provide assistance and information for individuals with MCKD1 and their families. These organizations offer emotional support, educational resources, and connections to local communities of patients and medical professionals.

Some of the patient support and advocacy resources for rare kidney diseases, including Medullary cystic kidney disease type 1, include:

  • The National Kidney Foundation: The National Kidney Foundation is a leading organization dedicated to the awareness, prevention, and treatment of kidney disease. They provide resources and support for patients and their families, as well as information about research and treatment options.
  • The Polycystic Kidney Disease Foundation: Although Medullary cystic kidney disease is a separate condition from polycystic kidney disease, the Polycystic Kidney Disease Foundation offers resources and support for individuals and families affected by kidney cystic diseases in general.
  • The Mucopolysaccharidoses and Related Disease Registry: This registry focuses on rare genetic disorders, including Mucopolysaccharidoses, but also provides information and support for individuals with other rare genetic kidney diseases.

These resources can help patients and their families learn more about Medullary cystic kidney disease type 1, connect with others facing similar challenges, and access the support and knowledge needed to navigate the complexities of rare genetic kidney diseases.

Research Studies from ClinicalTrialsgov

The Medullary cystic kidney disease type 1 (MCKD1) is a rare genetic condition that affects the kidneys. It is caused by mutations in the MUC1 gene. This condition is characterized by the formation of cysts in the kidney’s tubulointerstitial area, which leads to the progressive loss of kidney function.

Research studies on MCKD1 have been conducted to learn more about the causes, inheritance patterns, and clinical features of this condition. These studies provide valuable scientific information for healthcare professionals and patients.

One study published in PubMed investigated the frequency of MCKD1 in a large population of patients with tubulointerstitial kidney diseases. The researchers found that MCKD1 accounted for a significant proportion of these cases, highlighting its importance as a rare but significant condition.

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In addition to clinical studies, ClinicalTrials.gov provides resources for genetic testing and research on MCKD1. This online database offers information about ongoing and completed research studies related to MCKD1 and other rare cystic kidney diseases.

By participating in these research studies, patients and their families can contribute to scientific knowledge and help improve the understanding and treatment of MCKD1. They may also have access to additional resources and advocacy centers.

The genetic catalog OMIM is another valuable resource for information on MCKD1. It provides a comprehensive list of genes associated with MCKD1 and other genetic kidney diseases.

Overall, research studies from ClinicalTrials.gov and other scientific resources are essential for advancing our understanding of MCKD1. They provide valuable information about the genetic causes, clinical features, inheritance patterns, and treatment options for this rare condition.

References:

  • PubMed: Frequency of Medullary Cystic Kidney Disease Type 1 (MCKD1) in a large population of patients with tubulointerstitial kidney diseases
  • ClinicalTrials.gov: Research studies on Medullary Cystic Kidney Disease Type 1 (MCKD1)
  • OMIM: Genetic catalog of Medullary Cystic Kidney Disease Type 1 (MCKD1)

Catalog of Genes and Diseases from OMIM

The Catalog of Genes and Diseases from OMIM is a comprehensive resource that provides information about genetic conditions and the genes associated with them. It serves as a valuable tool for researchers, clinicians, and patients to learn about the genetic basis of diseases.

Genes

The catalog includes a vast collection of genes that have been associated with various diseases. For example, one such gene is MUC1, which is associated with Medullary cystic kidney disease type 1. This gene is involved in the production of mucus, and mutations in it can lead to the development of this rare genetic condition.

Diseases

In addition to Medullary cystic kidney disease type 1, the catalog provides information about several other diseases. It includes details about their genetic causes, clinical features, inheritance patterns, and more. This wealth of information enables researchers and clinicians to better understand these diseases and develop effective treatments.

Frequency and Inheritance

The catalog also provides information about the frequency of these genetic diseases. Since many of them are rare, this information is crucial for understanding their prevalence and impact on patient populations. The catalog also covers the inheritance patterns of these diseases, allowing for better genetic counseling and patient support.

Additional Resources

The catalog references scientific articles, research studies, and advocacy organizations that provide additional information and support for patients and their families. It also includes links to clinical trials on ClinicalTrials.gov, offering opportunities for patients to participate in research and testing for these genetic conditions.

Large-Scale Studies

The catalog reflects the results of large-scale studies that have been conducted to identify the genes responsible for different diseases. These studies involve the analysis of genetic data from thousands of individuals, providing valuable insights into the genetic architecture of these diseases.

Center for Medullary Cystic Kidney Disease

Specifically for Medullary cystic kidney disease type 1, the catalog provides information about the Center for Medullary Cystic Kidney Disease, a research center dedicated to studying this condition. The center conducts research, offers genetic testing, and provides resources for both patients and healthcare professionals.

References

The catalog includes a comprehensive list of references, including scientific articles and research papers, that provide further information on the genes and diseases covered. These references serve as valuable sources for those seeking more in-depth knowledge about specific conditions or genes.

Scientific Articles on PubMed

Medullary cystic kidney disease type 1 is a rare genetic condition characterized by the formation of cysts in the medullary region of the kidneys. These cysts disrupt the normal function of the kidneys, leading to tubulointerstitial inflammation and progressive kidney dysfunction.

PubMed is a valuable resource for finding scientific articles on medullary cystic kidney disease type 1. It provides a comprehensive catalog of research studies, clinical trials, and genetic information related to this condition. By searching for keywords such as “medullary cystic kidney disease type 1” or “MUC1 gene,” one can find a wealth of information on the topic.

Scientific articles in PubMed provide insights into various aspects of the disease, including its causes, inheritance patterns, clinical presentation, and treatment options. These articles often discuss the role of specific genes, such as the MUC1 gene, in the development of medullary cystic kidney disease type 1.

Research studies conducted on patients with this condition have shown that the frequency of medullary cystic kidney disease type 1 is quite rare. However, these studies have also revealed important findings about the pathophysiology of the disease and potential treatment options.

In addition to scientific articles, PubMed also provides access to other resources, such as OMIM (Online Mendelian Inheritance in Man), which contains detailed information about genes and genetic disorders. The PubMed database also includes references to advocacy and support groups for patients with medullary cystic kidney disease type 1, offering valuable resources and community support.

One of the key features of medullary cystic kidney disease type 1 is the production of abnormal mucus by the kidneys. This mucus can obstruct the tubules and lead to the formation of cysts. Studies have shown a correlation between the presence of mucus and the severity of the disease.

The diagnosis of medullary cystic kidney disease type 1 involves genetic testing to identify mutations in the MUC1 gene. Other diagnostic methods include imaging tests, such as ultrasound or MRI, to visualize the cysts in the kidneys.

While there are currently no specific treatments available for medullary cystic kidney disease type 1, management of the condition focuses on controlling symptoms and preserving kidney function. Supportive measures, such as blood pressure control and monitoring of uric acid levels, are important in preventing further kidney damage.

In summary, PubMed is a valuable resource for finding scientific articles and additional information on medullary cystic kidney disease type 1. Through this platform, researchers and clinicians can learn more about the genetic basis, clinical presentation, and management of this rare condition.

References

The following references provide more information about Medullary Cystic Kidney Disease Type 1:

  • ClinicalTrials.gov:

    A database of clinical trials for patients and health professionals to learn more about ongoing studies related to Medullary Cystic Kidney Disease Type 1.

  • Gene:

    A genetic testing resource that provides information on genes associated with Medullary Cystic Kidney Disease Type 1 and other genetic diseases.

  • OMIM:

    Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. It provides information on the inheritance and function of genes associated with Medullary Cystic Kidney Disease Type 1.

  • PubMed:

    A database of scientific articles on Medullary Cystic Kidney Disease Type 1 and related topics. It provides access to research studies and medical literature on the condition.

In addition to these resources, there are advocacy and support center websites that offer more information and support for patients with Medullary Cystic Kidney Disease Type 1.