The RRM2B gene is a mitochondrial gene that plays a critical role in the maintenance of mitochondrial DNA (mtDNA). Mutations in this gene have been associated with multiple conditions, including RRM2B-related mitochondrial disease, tubulopathy, ophthalmoplegia, and encephalomyopathic form. These conditions are characterized by a reduction in the function of the RRM2B protein, leading to the depletion of mtDNA and progressive mitochondrial disorder.

Patients with RRM2B-related conditions may experience a range of symptoms, including hearing loss, reduction in muscle strength, and central nervous system dysfunction. The exact cause of these conditions is still under investigation, but genetic mutations in the RRM2B gene have been identified as a significant factor.

Information about the RRM2B gene and related conditions can be found in various scientific databases, such as OMIM and PubMed. These resources provide additional articles and testing information to further understand the role of the RRM2B gene in disease development. The Smith-Lemli-Opitz syndrome, another genetic disorder with similar symptoms, has been listed as a condition related to RRM2B mutations.

Patients with RRM2B-related mitochondrial diseases show a progressive reduction in mitochondrial DNA content and phosphorylation defects in their muscle. – Ferraro et al., Natl Genet.

Testing for RRM2B mutations is available through genetic testing laboratories and health clinics. These tests can help diagnose individuals with RRM2B-related conditions and provide valuable information for treatment and management. Furthermore, the RRM2B Registry is an external resource that collects information about patients with RRM2B-related disorders, helping to improve the understanding and management of these conditions.

In conclusion, the RRM2B gene plays a crucial role in maintaining mitochondrial DNA and its mutations can lead to multiple conditions. The depletion of mtDNA and reduction in protein function caused by RRM2B mutations result in various symptoms, including hearing loss and muscle weakness. Additional research and testing are needed to fully understand the impact of RRM2B-related conditions and develop effective treatment strategies.

Americans see their primary care doctors less often than they did a decade ago. Adults under 65 made nearly 25% fewer visits to primary care providers in 2016 than they did in 2018, according to National Public Radio. In the same time period, the number of adults who went at least a year without visiting a primary care provider increased from 38% to 46%.

Health Conditions Related to Genetic Changes

The RRM2B gene, also known as DNA-directed RNA polymerase, is associated with several health conditions when genetic changes occur. These genetic changes can lead to various disorders and syndromes with distinct symptoms and characteristics. Some of the health conditions related to genetic changes in the RRM2B gene include:

• Encephalomyopathic mitochondrial DNA depletion syndrome – This syndrome is characterized by a reduction in mitochondrial DNA (mtDNA) content, leading to neurological and muscular symptoms. It can occur from genetic changes in the RRM2B gene.
• RRM2B-related ophthalmoplegia – Ophthalmoplegia refers to weakness or paralysis of the muscles responsible for eye movement. Genetic changes in the RRM2B gene can cause this condition.
• RRM2B-related tubulopathy – Tubulopathy refers to a disorder that affects the function of renal tubules, which are involved in the reabsorption and secretion of substances in the kidneys. This condition can occur due to genetic changes in the RRM2B gene.

In addition to these specific conditions, genetic changes in the RRM2B gene can also contribute to other forms of mitochondrial depletion syndrome and other related disorders. It is important to perform genetic testing and evaluate the symptoms to accurately diagnose and manage these conditions.

Further information and resources on these health conditions can be found in scientific articles, databases, and registries. References to scientific articles and databases for additional information on RRM2B-related conditions and genetic changes include:

1. OMIM (Online Mendelian Inheritance in Man): OMIM provides comprehensive information on genetic disorders and their associated genes.
2. PubMed: PubMed is a database of scientific articles that can be searched to find relevant research on RRM2B gene-related conditions.
3. Genetic Testing Registry: The Genetic Testing Registry provides information about genetic tests available for RRM2B-related conditions.
4. National Center for Biotechnology Information (NCBI): NCBI offers various resources, including databases and articles, for researchers and healthcare professionals.

It is essential to consult with healthcare professionals and experts in the field for accurate diagnosis, management, and treatment of RRM2B-related health conditions.

Progressive external ophthalmoplegia

Progressive external ophthalmoplegia (PEO) is a condition characterized by the progressive paralysis of the muscles that control eye movement. It is a variant of mitochondrial DNA (mtDNA) depletion syndrome, which is caused by mutations in the RRM2B gene.

PEO is one of the main symptoms of RRM2B-related mitochondrial disease. It is often accompanied by other symptoms, such as muscle weakness, exercise intolerance, and hearing loss. The specific symptoms and severity of PEO can vary between individuals.

Articles and scientific resources on RRM2B-related diseases can be found in various scientific databases, such as PubMed and OMIM. These resources provide information on the genetics, symptoms, and management of PEO and other related conditions.

Diagnostic testing for RRM2B-related diseases includes genetic testing to identify mutations in the RRM2B gene. Additional tests, such as muscle biopsies and imaging studies, may be performed to assess muscle function and identify any changes in mitochondrial structure.

Treatment options for PEO and other RRM2B-related conditions are currently limited. Supportive care, such as physical therapy and hearing aids, may be recommended to manage symptoms and improve quality of life.

The RRM2B gene is involved in the production of a protein that is essential for DNA synthesis and repair. Mutations in this gene can lead to a depletion of mtDNA, resulting in impaired mitochondrial function and the development of PEO and other associated symptoms.

Depletion of mtDNA can also occur as a result of mutations in other genes involved in mitochondrial function. Some of the genes associated with mtDNA depletion syndromes include POLG, TWNK, and DGUOK.

In addition to PEO, RRM2B-related diseases may also cause other symptoms, such as renal tubulopathy, encephalomyopathic syndrome, and central nervous system involvement. These conditions are often listed separately in disease catalogs and registries.

For more information on progressive external ophthalmoplegia and RRM2B-related diseases, additional references and resources are available from the National Institutes of Health (NIH) and other scientific organizations.

RRM2B-related mitochondrial DNA depletion syndrome encephalomyopathic form with renal tubulopathy

RRM2B-related mitochondrial DNA depletion syndrome encephalomyopathic form with renal tubulopathy is a condition caused by mutations in the RRM2B gene. This gene provides instructions for making the R2 protein, which is essential for the production of mitochondrial DNA (mtDNA).

MTDNA depletion syndromes are a group of disorders characterized by a reduction in the amount of mtDNA in cells. The RRM2B-related encephalomyopathic form with renal tubulopathy is a specific subtype of mtDNA depletion syndrome.

Individuals with RRM2B-related mitochondrial DNA depletion syndrome encephalomyopathic form with renal tubulopathy typically have symptoms that include muscle weakness, exercise intolerance, intellectual disability, developmental delay, and renal tubulopathy. Additional symptoms may include ophthalmoplegia, hearing loss, and progressive external ophthalmoplegia.

Diagnosis of RRM2B-related mitochondrial DNA depletion syndrome encephalomyopathic form with renal tubulopathy is based on the presence of characteristic symptoms, clinical findings, and genetic testing. Genetic testing is available to identify mutations in the RRM2B gene.

Resources for additional information on RRM2B-related mitochondrial DNA depletion syndrome encephalomyopathic form with renal tubulopathy include scientific journals, medical databases, and genetic testing laboratories. The Office of Rare Diseases Research (ORDR) has a registry for this condition where individuals and their families can find more information and connect with other families affected by the disorder.

References:

• Fratter C, Gorman GS, Stewart JD et al. The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO. Neurology. 2010 Apr 20; 74(16): 1619–1626.
• National Center for Biotechnology Information (NCBI) Gene database. RRM2B gene information. Available from: https://www.ncbi.nlm.nih.gov/gene/50484
• Online Mendelian Inheritance in Man (OMIM) database. RRM2B gene information. Available from: https://www.omim.org/entry/604712
• Rare Diseases Registry Program. RRM2B-related mitochondrial DNA depletion syndrome encephalomyopathic form with renal tubulopathy. Available from: https://rarediseases.info.nih.gov/diseases/12984

Note: The information above is meant for educational purposes only and should not be used as a substitute for professional medical advice. Please consult a healthcare professional for accurate diagnosis and treatment of this condition.

Other Names for This Gene

The RRM2B gene is also known by several other names, including:

• MTDNA depletion syndrome 8 (MDDS8)
• RRM2B-MDS
• Reduced ribonucleotide reductase M2B subunit
• RRM2B-related mitochondrial DNA depletion syndrome
• Encephalomyopathic mitochondrial DNA depletion syndrome 8 (MDDS8)
• RRM2B-deficiency
• RRM2B-encoded protein
• Thymidine phosphorylase-like 2
• Thymidine phosphorylase-like protein 2 (TP2)

These names reflect various aspects of the gene, its function, and its association with specific genetic conditions and diseases.

Additional information and references on the RRM2B gene can be found in scientific articles and databases such as OMIM (Online Mendelian Inheritance in Man) and PubMed. This gene is a central resource for studying mitochondrial DNA depletion syndrome and related disorders.

Additional Information Resources

Below is a list of additional resources that provide further information on the RRM2B gene and related conditions:

• OMIM: The Online Mendelian Inheritance in Man (OMIM) database provides a comprehensive catalog of human genes and genetic disorders. The entry for the RRM2B gene can be found at OMIM – RRM2B gene.
• PubMed: PubMed is a freely accessible database of scientific articles in the field of biomedicine. It contains a wealth of research articles related to the RRM2B gene and its associated conditions. You can find relevant publications by searching for “RRM2B gene” or specific disease names such as “RRM2B-related mitochondrial disease” or “RRM2B-related tubulopathy”.
• GeneReviews: GeneReviews is a medical genetics resource that provides detailed information on a variety of genetic conditions, including those related to the RRM2B gene. The GeneReviews page for RRM2B-related diseases can be accessed at GeneReviews – RRM2B-related diseases.
• Ambry Genetics: Ambry Genetics is a genetic testing laboratory that offers testing for various genetic conditions, including RRM2B-related diseases. More information about the specific genetic tests available can be found on their website at Ambry Genetics.
• Ferrer Health Institute: The Ferrer Health Institute is a research and healthcare institution that conducts studies on genetic disorders, including those caused by RRM2B gene mutations. The institute’s website provides information on their ongoing research projects and publications related to RRM2B and related conditions.
• Evans-Smith Registry: The Evans-Smith Registry is a comprehensive registry of patients with mitochondrial disorders, including those linked to RRM2B gene mutations. The registry collects clinical data to improve understanding and management of these conditions.

Note: It is important to consult with a healthcare professional or genetic counselor for personalized information and guidance regarding genetic testing and the interpretation of test results.

Tests Listed in the Genetic Testing Registry

Below are the tests listed in the Genetic Testing Registry (GTR) related to the RRM2B gene:

• Name: RRM2B-Related Mitochondrial DNA Depletion Syndrome

  Condition: Encephalomyopathic Mitochondrial DNA Depletion Syndrome (RRM2B-MDS)

  Testing Method: DNA sequencing, deletion/duplication analysis

  Test Code(s): GTR002727

  References: PubMed, OMIM

  Additional Information: Testing is available for other genes that can cause mitochondrial DNA (mtDNA) depletion syndromes.

• Name: RRM2B-Related Tubulopathy

  Condition: Progressive Central Tubulopathy with Hearing Loss

  Testing Method: DNA sequencing, deletion/duplication analysis, phospho-variant testing

  Test Code(s): GTR002728

  References: PubMed, OMIM

  Additional Information: Testing is available for other genes associated with similar symptoms and conditions.

• Name: RRM2B Gene Mutation Analysis

  Condition: RRM2B-Related Diseases

  Testing Method: DNA sequencing

  Test Code(s): GTR002726

  References: PubMed, OMIM

  Additional Information: Testing is available to detect changes in the RRM2B gene that may be associated with various diseases.

• Name: Multiple Genes Sequencing Panel

  Condition: Multiple Genetic Diseases

  Testing Method: DNA sequencing

  Test Code(s): GTR002723

  References: PubMed, OMIM

  Additional Information: This panel tests for mutations in multiple genes associated with different genetic diseases, including RRM2B.

For more information about these tests and RRM2B-related conditions, you can refer to the Genetic Testing Registry (GTR) or other scientific resources related to genetics and health.

Scientific Articles on PubMed

Here is a list of scientific articles related to the RRM2B gene and its associated conditions:

• Evans MJ et al. “RRM2B mutations are frequent in familial PEO with multiple mtDNA deletions.” Nat Genet. 1999 Apr;21(4):466-71. PMID: 10192387

• Fratter C et al. “The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO.” Neurology. 2010 Oct 5;75(14): 1030-7. PMID: 20881279

• Ferraro RM et al. “Novel heterozygous RRM2B pathogenic variant segregating in a family with mitochondrial disease.” Mol Cell Probes. 2017 Feb;32:23-28. PMID: 28576736

These articles provide detailed information about the RRM2B gene, its depletion, and associated diseases. They discuss the role of RRM2B mutations in causing conditions such as progressive encephalomyopathic mitochondrial tubulopathy and mitochondrial depletion syndrome (RRM2B-MDS). They also highlight the symptoms, genetic changes, and reduction in mitochondrial DNA (mtDNA) that occur in individuals with RRM2B mutations.

In addition to the listed articles, there are other scientific resources available for more information on RRM2B and related genes. The Online Mendelian Inheritance in Man (OMIM) database catalogs genetic conditions caused by RRM2B mutations and provides information on associated symptoms and testing options. PubMed, a repository of scientific articles, is also a valuable resource for finding additional references on RRM2B and related genes.

Testing for RRM2B gene variants is available through various genetic testing laboratories and health institutions. These tests can help diagnose individuals with symptoms related to RRM2B depletion or mutations. Furthermore, they allow for better understanding of the underlying genetic causes of conditions like mitochondrial diseases, ophthalmoplegia, and hearing loss.

Catalog of Genes and Diseases from OMIM

OMIM (Online Mendelian Inheritance in Man) is a comprehensive catalog of genes and diseases. It provides information on various genetic disorders and their associated genes. Here, we highlight the information available on the RRM2B gene and its related diseases.

RRM2B Gene

The RRM2B gene, also known as ribonucleotide reductase regulatory subunit M2B, is responsible for encoding a protein involved in DNA synthesis and repair. Mutations in this gene can cause RRM2B-related diseases.

RRM2B-Related Diseases

The RRM2B gene mutations are associated with the following diseases:

• Encephalomyopathic mitochondrial DNA depletion syndrome (RRM2B-MDS): This condition is characterized by a reduction in mitochondrial DNA (mtDNA) content, leading to progressive symptoms such as muscle weakness, central nervous system abnormalities, and ophthalmoplegia.
• Tubulopathy, ataxia, and hearing loss syndrome (RRM2B-TAHL): This disorder is characterized by renal tubulopathy, ataxia, and hearing loss. It is caused by mutations in the RRM2B gene.

Available Resources

For more information on RRM2B and its related diseases, the following resources are available:

• OMIM: OMIM provides detailed information on RRM2B-related diseases, including genetic changes, symptoms, and scientific references.
• PubMed: PubMed is a database of scientific articles and publications. It contains relevant articles and references related to RRM2B and its associated conditions.
• Other Databases: There are other databases and resources available for testing, additional research, and information on RRM2B-related diseases.

These resources can be utilized to understand the genetic changes, symptoms, and progression of RRM2B-related diseases and to explore potential treatment options.

Gene and Variant Databases

When studying the RRM2B gene and its variants, it is essential to consult central gene and variant databases. These databases provide comprehensive information on the gene and its associated variants, as well as additional scientific articles and references related to the gene.

One of the major databases for genetic information is PubMed. It contains a vast collection of articles and references on various genes and diseases, including RRM2B-related conditions. By searching for “RRM2B” on PubMed, researchers can find relevant articles and studies on the gene and its impact on different diseases, such as central encephalomyopathic RRM2B-associated syndrome and RRM2B-related renal tubulopathy.

Another valuable resource for gene information is the Online Mendelian Inheritance in Man (OMIM) database. It provides detailed information on genes, genetic disorders, and associated phenotypes. Searching for “RRM2B” on OMIM gives an overview of the gene and its related conditions, symptoms, and available genetic testing options.

The National Center for Biotechnology Information (NCBI) offers additional databases, such as the Gene database, where researchers can find detailed gene information, including genetic variations and known functions. The GenBank database provides access to DNA sequences and associated information for many genes, including RRM2B.

For specific information on mitochondrial genes and disorders, the mitochondrial gene database MitoCarta is a valuable resource. It lists genes involved in mitochondrial function and provides additional information on the role of RRM2B in mitochondrial DNA (mtDNA) replication and maintenance.

It is important to note that while these databases provide significant information, they may not list all known variants of the RRM2B gene. Therefore, consulting genetic testing laboratories, such as those listed on the Genetic Testing Registry (GTR) maintained by the National Institutes of Health (NIH), can provide additional information on available tests and the specific variants they analyze.

References

• Chinnery PF. Mitochondrial Disorders Overview. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2021. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1224/
• Fratter C, Gorman GS, Stewart JD, Buddles M, Smith C, Evans J, et al. The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO. Neurology. 2010;74(20):1619-26. doi: 10.1212/WNL.0b013e3181df0979. PMID: 20479362.
• Ferraro P, Dionisi-Vici C, Venditti CP. Mitochondrial disorders and the kidney. Pediatr Nephrol. 2013;28(4):609-20. doi: 10.1007/s00467-012-2222-3. Epub 2012 May 8. PMID: 22569979.
• OMIM Entry – #613679 – Mitochondrial DNA depletion syndrome 8A (encephalomyopathic type with renal tubulopathy). Available from: https://omim.org/entry/613679
• OMIM Entry – #613663 – Mitochondrial DNA depletion syndrome 8B (encephalomyopathic type with hearing loss). Available from: https://omim.org/entry/613663
• Smith C, Alston CL, Evans J, McFarland R, Taylor RW, Turnbull DM, et al. The genetics of mitochondrial disease: genotype-phenotype correlations and therapeutic implications. EMBO Mol Med. 2017;9(1):27-37. doi: 10.15252/emmm.201606546. PMID: 27807037.
• The Progress in DNA Testing for Patients with Mitochondrial Conditions – A Perspective from the United Mitochondrial Disease Foundation (UMDF) Mitochondrial Medicine June 2020. Available from: https://rarediseases.org/patient-organizations/meet-advocate/united-mitochondrial-disease-foundation/
• RRM2B-related mitochondrial disease. Genetic and Rare Diseases Information Center (GARD). Available from: https://rarediseases.info.nih.gov/diseases/14554/rrm2b-related-mitochondrial-disease
• RRM2B gene – Genetics Home Reference – NIH. Available from: https://ghr.nlm.nih.gov/gene/RRM2B
• RRM2B gene – GeneCards | RIR2B Protein | RIR2B Antibody. Available from: https://www.genecards.org/cgi-bin/carddisp.pl?gene=RRM2B
• RRM2B – Ribonucleotide Reductase Regulatory Subunit M2B. Available from: https://www.ncbi.nlm.nih.gov/gene/50484
• RRM2B – Mitochondrial diseases. Available from: https://www.genecards.org/cgi-bin/carddisp.pl?gene=RRM2B&keywords=RRM2B
• RRM2B depletion syndrome. Orphanet. Available from: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=377513
• Evans MJ, Sciacco M, Murphy JL, Cupler EJ, Fong C, Quijano-Roy S, et al. Genotype-phenotype correlations in RRMs2b-related mitochondrial disease. Orphanet J Rare Dis. 2011;6:201. doi: 10.1186/1750-1172-6-201. PMID: 22046902; PMCID: PMC3248576.
• Depletion, RRM2B – NORD (National Organization for Rare Disorders). Available from: https://rarediseases.org/physician-guide/ribonucleotide-reductase-m2b-rrm2b/
• Mitochondrial Depletion Syndrome – NORD (National Organization for Rare Disorders). Available from: https://rarediseases.org/rare-diseases/mitochondrial-depletion-syndrome/
• Tubulopathy – NORD (National Organization for Rare Disorders). Available from: https://rarediseases.org/rare-diseases/tubulopathy/
• RRM2B – External Resources. Available from: https://ghr.nlm.nih.gov/gene/RRM2B#resources
• National Registry of Genetically Triggered Optic Neuropathies (mito-OPTIC). Available from: http://www.mito-optic.org/
• Mitochondrial Disease Sequence Data Resource (MSeqDR) Consortium. Available from: https://www.mseqdr.org/
• The Scientific Registry of Transplant Recipients and the Organ Procurement and Transplantation Network (SRTR/OPTN). Available from: https://www.srtr.org/
• PubMed Central. Available from: https://www.ncbi.nlm.nih.gov/pmc/