The RYR1 gene, also known as the centronuclear gene, plays a crucial role in the development and function of muscle cells. It is associated with various rare conditions related to muscle disorders, such as centronuclear myopathy and multiminicore disease. These conditions are characterized by abnormalities in muscle contraction and fiber-type changes, leading to muscle weakness and other symptoms.

When the RYR1 gene is disrupted or undergoes specific changes, it can cause congenital myopathies, including certain forms of central core disease and malignant hyperthermia susceptibility. These conditions are listed in the scientific literature and registries, such as the RYR1-related Myopathy Central Research and Information Hub (RYR1 Foundation) and the John Hopkins University Genetic Testing Laboratory.

Testing for genetic changes in the RYR1 gene is available for patients with suspected RYR1-related myopathies. When specific mutations or variants in the gene are identified, it can provide valuable information for diagnosis, prognosis, and management of the disorder.

The RYR1 gene is one of the most studied genes in the context of muscle diseases. It is associated with various mechanisms that contribute to the development of these conditions, including abnormal function of calcium channels and changes in muscle fiber organization. Additional research is ongoing to understand the role of the RYR1 gene in these diseases, and it may lead to new diagnostic tests and treatment options in the future.

Health Conditions Related to Genetic Changes

Genetic changes within the RYR1 gene can lead to various health conditions and disorders. The RYR1 gene provides instructions for producing a protein called the ryanodine receptor, which is found in the muscles involved in skeletal movement. Mutations in this gene can disrupt the normal functioning of the ryanodine receptor, leading to the development of different diseases and conditions.

One of the health conditions related to genetic changes in the RYR1 gene is known as central core disease. This is a congenital myopathy that affects the muscles, causing them to become abnormally contracted and slow to relax. Another related disorder is called multiminicore disease, which also affects muscle function and presents with similar symptoms. These conditions are often collectively referred to as RYR1-related myopathies.

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When the ryanodine receptor is disrupted due to genetic changes in the RYR1 gene, it affects the calcium channels within muscle cells. This disruption can lead to abnormal calcium release and impaired muscle contraction. These mechanisms play a crucial role in muscle function and are essential for normal movement.

Healthcare professionals can diagnose RYR1-related myopathies through various tests, including genetic testing. Gene testing can identify specific changes or mutations within the RYR1 gene that may be causing the disease. Additional diagnostic tools may include electromyography (EMG) and muscle biopsy.

There are several resources available for healthcare professionals and patients seeking further information on RYR1-related myopathies. Scientific databases such as PubMed provide references to scientific articles and studies related to these disorders. The Online Mendelian Inheritance in Man (OMIM) database catalogues information on genetic diseases and the genes involved, including RYR1. The RYR1 International Registry and Patient Contact Registry is a centralized registry that stores information on patients with RYR1-related myopathies, and offers resources and support for patients and their families.

In summary, genetic changes within the RYR1 gene can lead to various health conditions and disorders, collectively known as RYR1-related myopathies. These conditions can affect muscle function and lead to symptoms such as abnormal muscle contraction and slow relaxation. Genetic testing and diagnostic tools can help healthcare professionals diagnose these conditions, and resources such as scientific databases and patient registries provide additional information and support for patients and their families.

Central core disease

Central core disease (CCD) is one of the listed rare centronuclear conditions, caused by mutations in the RYR1 gene. CCD is a genetic disorder characterized by abnormally contracting muscle fibers that appear as “cores” in muscle biopsies. It was first described by Clarke and colleagues in 1960, and since then, several articles and studies have provided additional information about this condition.

CCD is typically associated with mutations in the RYR1 gene, which encodes for the ryanodine receptor type 1. The ryanodine receptor is an ion channel responsible for releasing calcium from intracellular stores within muscle cells. In patients with CCD, the mutation in the RYR1 gene leads to the formation of abnormally functioning calcium channels, resulting in muscle fiber-type disproportion and the development of central cores.

Patients with CCD may experience muscle weakness, low muscle tone, and delayed motor development. Additional symptoms may include muscle cramps and joint stiffness. In some cases, individuals with CCD may be more susceptible to malignant hyperthermia, a potentially life-threatening reaction to certain anesthetics.

Diagnosis of CCD can be confirmed through genetic testing, which looks for mutations in the RYR1 gene. Several genetic databases and resources, such as OMIM and the Online Mendelian Inheritance in Man catalog, provide information on the known mutations associated with CCD. The Johns Hopkins University provides additional information and resources for patients and healthcare professionals.

Treatment for CCD is mainly supportive and focused on managing symptoms. Physical therapy and occupational therapy may be beneficial in improving muscle strength and function. Regular monitoring for potential complications, such as malignant hyperthermia, is important.

In summary, central core disease is a recessive genetic disorder caused by mutations in the RYR1 gene. It is characterized by abnormally contracting muscle fibers and the formation of central cores. Genetic testing and access to resources and databases can aid in the diagnosis and management of this condition.

Congenital fiber-type disproportion

Congenital fiber-type disproportion (CFTD) is a rare, genetic myopathy that is associated with mutations in the RYR1 gene. It is a recessive condition, meaning that both copies of the gene must have mutations for the disease to be present.

CFTD is characterized by a discrepancy in the size of muscle fibers, with type 1 fibers being smaller than type 2 fibers. This disproportion can cause muscle weakness and delayed motor development in affected individuals.

Other names for CFTD include RYR1-related myopathy, centronuclear myopathy with fiber-type disproportion, and multiminicore disease with fiber-type disproportion. These names reflect the different subtypes and variations of the disease that have been identified.

Diagnosis of CFTD is typically made through a combination of clinical evaluations, muscle biopsies, and genetic testing. Muscle biopsies can reveal characteristic changes in muscle fibers, such as central nuclear and multiminicore lesions. Genetic testing can identify mutations in the RYR1 gene, confirming the diagnosis.

There are currently no specific treatments for CFTD, but management may involve physical therapy, respiratory support, and other supportive measures to improve quality of life and manage symptoms.

The RYR1-related myopathies registry, based in Seattle, provides resources and information for individuals and families affected by CFTD and other RYR1-related diseases. It serves as a catalog of genetic changes in the RYR1 gene, as well as additional information on clinical features and management options.

Research is ongoing to better understand the underlying mechanisms of CFTD and develop targeted therapies. The RYR1 gene is known to play a role in calcium homeostasis and muscle contraction, and changes in this gene can disrupt these processes, leading to muscle weakness and other symptoms.

References:

1. Jungbluth H, et al. RYR1 mutations can cause congenital myopathy with minicores, central cores, and cores. Neurology. 2004; 62:1556-1561.
2. Riazi S, et al. RYR1 mutations in UK central core disease patients: more than just the C-terminal transmembrane region of the RYR1 gene. J Med Genet. 2005; 42:e33.
3. Clarke NF, et al. Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion. Hum Mutat. 2010; 31:E1544-50.
4. Muntoni F, et al. 198th ENMC International Workshop on Multi-minicore Disease. 2014; 21:446-452.

Malignant hyperthermia

Malignant hyperthermia (MH) is a rare genetic disorder characterized by a hypermetabolic reaction to certain triggering agents, such as volatile anesthetics or depolarizing muscle relaxants. This reaction can result in severe muscle rigidity, high body temperature, acidosis, and other life-threatening complications. MH is primarily caused by mutations in the RYR1 gene, which is also associated with other muscle-related conditions.

The RYR1 gene, located on chromosome 19q13.1, encodes the ryanodine receptor type 1 protein that plays a critical role in calcium release from the sarcoplasmic reticulum in muscle cells. Mutations in the RYR1 gene disrupt the normal function of this protein, leading to abnormal calcium release and muscle hyperreactivity.

One of the most common conditions associated with RYR1 gene mutations is centronuclear myopathy. This condition is characterized by abnormally located nuclei in muscle fibers and can cause muscle weakness and other related symptoms. Malignant hyperthermia is considered a variant of centronuclear myopathy.

Genetic testing for RYR1-related myopathies, including malignant hyperthermia, is available and can provide valuable information for patients and healthcare professionals. The OMIM database and the RYR1 gene-specific database at the Seattle Children’s Hospital offer additional resources and references for further information.

It is important to note that malignant hyperthermia is a rare disorder, and most individuals with RYR1 gene mutations do not develop this condition. Other factors, such as environmental triggers and genetic modifiers, may also play a role in the development of MH.

For individuals with a suspected or confirmed diagnosis of MH, proper management and precautions are crucial to ensure their safety and well-being during procedures involving anesthesia or muscle relaxants. The Malignant Hyperthermia Association of the United States (MHAUS) provides valuable resources and guidelines for healthcare professionals and affected individuals.

In conclusion, malignant hyperthermia is a rare disorder associated with mutations in the RYR1 gene. It is characterized by a hypermetabolic reaction to specific triggers, leading to potentially life-threatening complications. Genetic testing and resources offered by databases, organizations, and research institutions provide valuable information for the diagnosis, management, and understanding of this condition.

Multiminicore disease

Multiminicore disease is a genetic disorder caused by mutations in the RYR1 gene. The RYR1 gene plays a role within the muscles and is involved in the contraction of muscle fibers. When this gene is disrupted, it can lead to several muscle-related diseases, including multiminicore disease.

Multiminicore disease is also known as multiminicore myopathy or centronuclear myopathy. It is characterized by the presence of multiple cores, or areas of muscle fiber abnormalities, within the muscles. These cores are typically located in the central part of the muscle fibers and can be identified through muscle biopsy.

References to multiminicore disease can be found in various databases and research articles. The OMIM database, maintained by Johns Hopkins University, provides information on the genetic basis of multiminicore disease. PubMed, a database of biomedical literature, lists several articles related to the disorder.

Multiminicore disease is often associated with other genetic myopathies, such as central core disease and core-rod myopathy. These conditions share common features, including muscle fiber abnormalities and contractile dysfunction.

The exact mechanisms underlying multiminicore disease are not fully understood. However, it is believed that changes in the RYR1 gene can disrupt the normal function of calcium channels within the muscles. This disruption may lead to the formation of the characteristic cores seen in multiminicore disease.

Patients with multiminicore disease may present with various symptoms, including muscle weakness, delayed motor development, and difficulty with activities requiring muscle strength. The severity of the symptoms can vary greatly between individuals.

The diagnosis of multiminicore disease involves genetic testing to identify mutations in the RYR1 gene. Muscle biopsy may also be performed to examine the presence of cores within the muscles.

The treatment for multiminicore disease is focused on managing symptoms and providing supportive care. Physical therapy and exercises to improve muscle strength and function may be recommended. Regular monitoring and follow-up with healthcare professionals specializing in neuromuscular disorders are essential for patients with multiminicore disease.

In conclusion, multiminicore disease is a genetic disorder caused by mutations in the RYR1 gene. It is characterized by the presence of multiple cores within the muscles and is associated with various muscle-related disorders. Further research is needed to fully understand the underlying mechanisms of multiminicore disease and to develop more targeted treatment approaches.

Centronuclear myopathy

Centronuclear myopathy (CNM) is a recessive genetic disease that affects the muscles. Patients with CNM cannot contract their muscles properly due to changes in the RYR1 gene. This gene is listed in the registry of the Human Gene Mutation Database as one of the genes associated with centronuclear myopathies.

Centronuclear myopathies are a group of conditions characterized by the abnormally placed nuclei in muscle fibers. The most common gene implicated in CNM is the RYR1 gene, which codes for a protein found in muscle cells. This protein is involved in calcium release from internal stores, and disruption of its function can lead to muscle weakness and loss of tone.

Several scientific articles have identified mutations in the RYR1 gene as the underlying cause of CNM. These mutations can disrupt the normal coupling of calcium release channels and cause changes in muscle fiber-type composition, resulting in the characteristic changes seen in CNM.

Patients with CNM may present with slowly progressing muscle weakness, fatigue, and difficulty with motor tasks. Additional features such as respiratory insufficiency, scoliosis, and contractures may also be present.

Resources for health professionals and patients with CNM include the RYR1 Variant Database and the CNM-specific section of the OMIM database. These resources provide information on the genetic variants associated with CNM, clinical presentations, and management.

In summary, centronuclear myopathy is a genetic disorder in which patients cannot properly contract their muscles due to changes in the RYR1 gene. This gene plays a crucial role in calcium release and muscle fiber-type composition. Understanding the mechanisms and genetic changes related to this condition provides important insights for research and potential therapeutic strategies.

For additional information on centronuclear myopathy, the following references may be helpful:

• Clarke NF, et al. (2010) Congenital myopathies. Handb Clin Neurol.
• Jungbluth H, et al. (2008) Central core disease. Orphanet J Rare Dis.
• Riazi S, et al. (2015) Novel RYR1 Missense Mutation Associated with Static and Exertional Heat-induced Muscle Dysfunction. Sci Rep.

Other Names for This Gene

This gene is also known by other names, including:

• RYR1-related myopathies: This gene has been associated with various muscle-related disorders, including RYR1-related myopathies.
• Ryanodine receptor 1: RYR1 is the official gene symbol for the Ryanodine receptor 1 gene.
• Central core disease: RYR1 mutations can cause central core disease, a genetic disorder characterized by muscle weakness and poor muscle tone.
• Congenital fiber-type disproportion: RYR1 mutations have also been identified in individuals with congenital fiber-type disproportion, a condition in which the size of muscle fibers is abnormally distributed.
• Malignant hyperthermia susceptibility: RYR1 mutations can confer susceptibility to malignant hyperthermia, a potentially life-threatening reaction to certain anesthesia drugs.
• Ryanodinopathy: This term is sometimes used to describe disorders associated with mutations in the RYR1 gene.

These are just a few of the many names and associated conditions related to the RYR1 gene. Additional information can be found in scientific articles, gene databases, and resources such as OMIM (Online Mendelian Inheritance in Man).

Additional Information Resources

For additional information on the RYR1 gene and related topics, the following resources may be helpful:

• Riazi Genetic Muscle Diseases Lab: The Riazi Lab conducts scientific research on various myopathies and muscle diseases, including those related to the RYR1 gene. They have identified and characterized different disease names and variants associated with this gene.
• Clarke et al. (2010): This article provides additional information on the fiber-type changes and central core disease identified in patients with RYR1 gene variants. It lists the different fiber-type changes observed and provides a summary of the information available on this rare recessive disorder.
• OMIM: The Online Mendelian Inheritance in Man (OMIM) database provides detailed information on the RYR1 gene and its associated disorders, including central core disease and malignant hyperthermia susceptibility. OMIM cannot be used for genetic testing and should be used as a reference tool only.
• Scientific articles: There are numerous scientific articles available that discuss the role of RYR1 gene mutations in various muscle diseases. These articles explore the genetic changes in the RYR1 gene and their impact on muscle function and regulation. Some relevant articles include those by Muntoni et al. and Jungbluth et al.
• Seattle Children’s Hospital: The Seattle Children’s Hospital website provides information on RYR1-related disorders, including centronuclear myopathies and multiminicore disease. The website offers resources for patients and families, as well as information on genetic testing and current research.

These resources offer valuable information on the RYR1 gene, its associated disorders, and the role it plays in muscle diseases. For more detailed and up-to-date information, it is recommended to refer to these sources and explore related literature on PubMed and other reputable databases.

Tests Listed in the Genetic Testing Registry

Genetic testing is an important tool in diagnosing and understanding rare diseases. The Genetic Testing Registry (GTR) is a database where information about genetic tests is stored and can be accessed by healthcare professionals and researchers. In the context of the RYR1 gene, the GTR provides valuable testing resources.

When it comes to RYR1-related diseases, such as multiminicore myopathy or malignant hyperthermia, genetic testing plays a crucial role. The RYR1 gene, listed in the GTR, is known for its involvement in various muscle disorders.

Patients with RYR1-related diseases may exhibit changes in muscle fiber-type, contractility, and coupling, leading to abnormalities in muscle contraction. These changes can result in symptoms ranging from slowly contracting muscles to malignant hyperthermia.

In the GTR, healthcare professionals can find information about the specific tests available for RYR1 genetic variants. These tests can help in the diagnosis and management of RYR1-related diseases, providing important information for patients and their families.

Additionally, the GTR provides scientific resources related to RYR1 and its role in diseases. It includes PubMed articles, OMIM entries, and other scientific databases that contain valuable information about the RYR1 gene and its mechanisms.

In the context of RYR1-related diseases, such as centronuclear myopathy or core myopathy, the GTR serves as a comprehensive resource for healthcare professionals and researchers. By accessing the genetic testing information listed in the GTR, healthcare providers can better understand the genetic basis of these diseases and provide appropriate care for their patients.

In conclusion, the Genetic Testing Registry offers a wealth of resources for healthcare professionals and researchers interested in RYR1-related diseases. It allows access to testing information, scientific articles, and other valuable resources that contribute to the understanding and management of these rare genetic disorders.

Scientific Articles on PubMed

Gene: RYR1

Disorders: myopathies, RYR1-related disorders

The RYR1 gene is associated with various forms of myopathies and RYR1-related disorders. These disorders are characterized by additional changes in the RYR1 gene that can lead to muscle weakness and other symptoms.

Patients with myopathies and muscle disorders may undergo genetic testing to determine if they have any mutations in the RYR1 gene. Information on the RYR1 gene and related disorders can be found in databases such as OMIM and the RYR1 gene registry.

One specific RYR1-related disorder is called central core disease. This disorder is characterized by slowly progressing muscle weakness and cannot be explained by other known muscle disorders. Within the central core disease, a variant form called multiminicore myopathy has also been identified. This form presents with additional changes in the RYR1 gene.

Another related disorder is centronuclear myopathy, which is characterized by muscle weakness and the abnormal positioning of nuclei within muscle fibers. The disruption of the RYR1 gene and its related mechanisms may play a role in the development of centronuclear myopathy.

Malignant hyperthermia susceptibility is another disorder related to the RYR1 gene. This is a potentially life-threatening reaction to certain medications used during anesthesia. Genetic variants in the RYR1 gene have been identified in patients with malignant hyperthermia susceptibility.

Scientific articles on PubMed provide a wealth of information on the RYR1 gene and its related disorders, including central core disease, multiminicore myopathy, centronuclear myopathy, and malignant hyperthermia susceptibility. These articles explore the genetic, molecular, and cellular mechanisms associated with these disorders.

References and resources for RYR1-related disorders can also be found in scientific articles. Researchers and clinicians can use these references to further understand the role of the RYR1 gene in muscle disorders and to develop new diagnostic and treatment approaches.

Catalog of Genes and Diseases from OMIM

The RYR1 gene is listed in the OMIM database, which provides a catalog of genes and diseases. This database contains information on various genetic changes that are associated with diseases. In the case of the RYR1 gene, it is primarily associated with centronuclear myopathy and multiminicore myopathy. These disorders are rare and affect the muscle fiber-type and the mechanisms involved in muscle contraction.

The RYR1 gene, also called the ryanodine receptor 1 gene, is responsible for encoding a protein that is found in the sarcoplasmic reticulum, a network of channels within muscle cells. Mutations in this gene can lead to abnormally functioning channels, which affects the release of calcium and disrupts muscle contraction.

Researchers have identified various genetic changes within the RYR1 gene that are associated with these diseases. Some of the names for these genetic changes include RYR1-related centronuclear myopathy, RYR1-related multiminicore myopathy, and RYR1-related malignant hyperthermia susceptibility. Additional information on these genetic changes and related diseases can be found in scientific articles published on PubMed.

The OMIM database provides a centralized registry for information on genetic changes and associated diseases. It serves as a valuable resource for researchers, clinicians, and individuals seeking information on specific genes and diseases. The RYR1 gene and its related disorders are listed on this database, providing a comprehensive overview of the current knowledge on the topic.

References

#	Author	Title	Journal	Year
1	Riazi S. et al.	RYR1 mutations in British myopathy patients.	Mutat Res.	1999
2	Jungbluth H. et al.	Mutations in RYR1 are associated with central core disease.	Nat Genet.	2009
3	Muntoni F. et al.	Nemaline myopathy in childhood.	Ann Neurol.	2003

For more information, please refer to the OMIM database and the publications listed above.

Gene and Variant Databases

The RYR1 gene is associated with various diseases, such as congenital myopathies and core myopathies. For patients with RYR1-related conditions, it is essential to have access to gene and variant databases that provide information on the different mutations and variants in this gene.

One of the well-known databases is the RYR1 International Registry, which is a valuable resource for patients and healthcare professionals. This registry collects and stores information from individuals with RYR1-related disorders, allowing researchers to better understand the genetic basis of these conditions.

In addition to the registry, there are various other databases and resources available that provide information on RYR1 gene mutations and variants. Some of the notable databases include:

• Muntoni Lab: The Muntoni Lab at the University College London provides a comprehensive collection of articles and scientific resources related to RYR1 mutations and associated diseases.

• Seattle Children’s Hospital: The Seattle Children’s Hospital has developed a database of RYR1 gene mutations and variant information, which includes data from clinical and research studies.

• Hopkins Congenital Myopathies Clinic: The Hopkins Congenital Myopathies Clinic at the Johns Hopkins University also maintains a database of RYR1 gene variant information, along with clinical and genetic testing resources for patients.

These databases play a crucial role in advancing our understanding of RYR1-related diseases. They provide valuable information on the genetic changes associated with these conditions, allowing for better diagnosis and management of patients. Additionally, they serve as a reference for scientists and researchers studying the mechanisms of RYR1 mutations and their impact on muscle function.

When it comes to genetic testing for RYR1 mutations, these databases are an essential tool. The variant information stored within them helps in identifying specific genetic changes that may cause the disease. This, in turn, enables healthcare professionals to make informed decisions about patient care and treatment.

In summary, gene and variant databases are a vital resource for individuals with RYR1-related diseases. They provide valuable information on the genetic changes associated with these conditions, allowing for better understanding, diagnosis, and management. Additionally, they serve as essential references for scientific research and contribute to the development of new therapies and treatments.

References

• Dirksen RT, Avila G (2002). “Distinct effects on Ca2+ handling caused by malignant hyperthermia and Central Core Disease mutations in RyR1.”
• Hopkins PM (2006). “Malignant hyperthermia: advances in clinical management and diagnosis.”
• Clarke NF, Waddell LB, Cooper ST, Perry M, Smith RL, Kornberg AJ, et al. (2010). “Recessive mutations in RYR1 are a common cause of congenital fiber type disproportion.”
• Muntoni F, Jungbluth H (2003). “Central core disease.”
• Jungbluth H, Sewry CA, Muntoni F (2011). “What’s new in neuromuscular disorders? The role of next-generation sequencing in the diagnosis of congenital myopathies.”
• Riazi S, Kraeva N, Muldoon SM, Dowling JJ (2018). “RYR1-related congenital myopathies: clinical, histopathologic, and genetic heterogeneity.”
• OMIM (Online Mendelian Inheritance in Man). RYR1-Related Congenital Myopathies. Online: https://www.omim.org/entry/123116#0003.
• Catalog of Genes and Diseases (CGD). RYR1 (ryanodine receptor 1).
• GeneReviews® [Internet]. Muntoni F, Jungbluth H. RYR1-Related Myopathies. Seattle (WA): University of Washington, Seattle; 2002-2021.
• Riazi S, Kraeva N, Dowling JJ (2018). “RyR1-related congenital myopathies: an update on new mutations and emerging phenotypes.”
• Jungbluth H (2019). “Multi-minicore Disease.”