The MT-TL1 gene, also known as the Mitochondrially Encoded TRNA Leucine 1 (UUA/G) gene, is a gene that is involved in the production of a specific type of RNA molecule called transfer RNA (tRNA). This gene is located in the mitochondrial genome and plays a crucial role in the mitochondria’s ability to produce energy for the cell.

Alterations or mutations in the MT-TL1 gene have been linked to various disorders, including myoclonic epilepsy with ragged-red fibers (MERRF), a neurological condition characterized by myoclonic seizures, muscle weakness, and ragged-red fibers in muscle tissue. These mutations result in the production of abnormal tRNA molecules, which impair the mitochondria’s ability to produce energy effectively.

In addition to MERRF, mutations in the MT-TL1 gene have also been associated with other mitochondrial diseases, such as Leigh syndrome, encephalomyopathy, and cardiomyopathy. These conditions can cause a range of symptoms, including neurological deficits, muscle weakness, hearing loss, and even potentially life-threatening complications.

Research into the MT-TL1 gene and its role in mitochondrial diseases is ongoing. Scientists are working to understand how specific mutations in this gene contribute to the development of these conditions and to develop potential treatment options. Understanding the molecular mechanisms and genetic changes associated with mitochondrial diseases like MERRF can provide valuable insight into the underlying causes and potential therapeutic targets for these conditions.

Health Conditions Related to Genetic Changes

In the context of the MT-TL1 gene, several health conditions can be related to genetic changes. These changes can occur at the molecular level, affecting the chemical composition and functioning of certain genes. One such condition is myoclonic epilepsy with ragged-red fibers (MERRF), which is characterized by myoclonic seizures, muscle weakness, and other neurological features.

These genetic changes are typically inherited maternally, as the MT-TL1 gene is located in the mitochondrial DNA. Mitochondria are responsible for energy production in cells and are involved in various biological processes. Mutations in the MT-TL1 gene can disrupt the assembly of mitochondrial proteins, leading to deficiencies in energy production and causing health conditions.

Just under half – 49% – of Americans get their health insurance through their employer, according to the Henry J. Kaiser Family Foundation. Another 19% of Americans are insured under Medicaid, 14% under Medicare, seven% under non-group plans and two% under other public insurers, while nine% of U.S. citizens remain uninsured.

One of the health conditions related to genetic changes in the MT-TL1 gene is Leigh syndrome, a progressive neurological disorder characterized by severe neurological and neuromuscular abnormalities. This condition can lead to stroke-like episodes and affects various parts of the central nervous system.

Another health condition related to genetic changes in the MT-TL1 gene is deafness and dystonia syndrome, which is characterized by hearing loss and abnormal muscle contractions. This condition can also involve other neurological symptoms such as seizures and movement disorders.

There are several resources available to explore and understand these genetic changes and the health conditions they can cause. The Mitochondrial Disease Registry is a comprehensive database that catalogues information about different mitochondrial diseases and their related genetic mutations. Scientific articles and research papers available on websites like PubMed and OMIM provide valuable insights into the genetic and molecular mechanisms involved in these conditions.

The ability to transfer genetic information across generations plays a significant role in understanding and managing these health conditions. Genetic counseling and testing can help individuals identify whether they carry certain genetic variants that could contribute to these conditions. This information allows individuals to make informed decisions about their health and plan for appropriate medical care.

Maternally inherited diabetes and deafness

Maternally inherited diabetes and deafness is a condition that is caused by mutations in the MT-TL1 gene. This gene is located in the mitochondrial DNA (mtDNA), which is inherited from the mother. Mutations in the MT-TL1 gene can result in a variety of symptoms, including diabetes and hearing loss.

Turnbull et al. first described this condition in 1990 and named it “maternally inherited diabetes and deafness” (MIDD). They found that individuals with MIDD have a specific mutation in the MT-TL1 gene, which affects the production of the protein needed for proper mitochondrial function.

MIDD is a complex disorder and its symptoms can vary among affected individuals. In addition to diabetes and deafness, some individuals may also experience episodes of myoclonic epilepsy. Other symptoms can include ophthalmoplegia (weakness or paralysis of the eye muscles), encephalomyopathy (a progressive disorder affecting the brain and muscles), and cardiomyopathy (a disease of the heart muscle).

Diagnosis of MIDD can be challenging, as it requires genetic testing to identify mutations in the MT-TL1 gene. Additionally, certain clinical tests and imaging studies may be performed to evaluate the extent of organ involvement. For example, a muscle biopsy may show characteristic features such as ragged-red fibers.

Treatment for MIDD is primarily focused on managing the symptoms and complications associated with the condition. This can include the use of medications to control blood sugar levels in individuals with diabetes and hearing aids or cochlear implants to improve hearing in those with hearing loss. Regular monitoring and follow-up with a healthcare provider are important to ensure optimal management of the condition.

Research into the underlying mechanisms of MIDD is ongoing, and scientists are continuing to investigate the role of the MT-TL1 gene and other related genes in mitochondrial function and disease. These studies may provide further insights into the development of potential treatments or interventions for MIDD.

References

1. Turnbull DM, et al. (1990) Mitochondrial DNA mutations in human colonic crypt stem cells. J Clin Invest. 86(1):20-5.
2. OMIM entry for Maternally Inherited Diabetes and Deafness; MIDD. Available at: https://omim.org/entry/520000
3. Additional resources on mitochondrial genetic disorders. Health Resources and Services Administration. Available at: https://www.hrsa.gov/advisory-committees/mchba/meetings/2021/2021-05-18/summary-slides/mito.pdf
4. Catalog of Genes and Diseases. National Center for Biotechnology Information. Available at: https://www.ncbi.nlm.nih.gov/catalog/Gene
5. Mitochondrial DNA assembly and genetic testing. U.S. National Library of Medicine. Available at: https://ghr.nlm.nih.gov/primer/mtdna/testing

Mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes

Mitochondrial encephalomyopathy lactic acidosis and stroke-like episodes (MELAS) is a rare genetic disorder that affects the mitochondria, the energy-producing structures in cells. It is caused by mutations in the MT-TL1 gene, which is found in mitochondrial DNA (mtDNA).

MELAS is inherited maternally, which means it is passed down from the mother to her children. A person with MELAS may have a certain variant of the MT-TL1 gene that is responsible for the condition. This variant can cause problems in the assembly and transfer of proteins that are necessary for the normal function of mitochondria.

The symptoms of MELAS vary from person to person, but the most common features listed in medical articles include stroke-like episodes, encephalopathy (a brain disorder), seizures, muscle weakness or stiffness, and cardiac abnormalities. Additional symptoms can include hearing loss (deafness), ophthalmoplegia (weakness or paralysis of eye muscles), and lactic acidosis (buildup of lactic acid in the body).

Diagnosis of MELAS usually involves genetic testing to identify changes or mutations in the MT-TL1 gene. This can be done by analyzing a person’s DNA for specific changes or by testing muscle tissue for abnormalities in mitochondrial function.

There is no cure for MELAS, but treatment focuses on managing symptoms and supporting overall health. This may include medications to control seizures, physical therapy to improve muscle strength and mobility, and cardiac monitoring to identify and manage any heart-related issues.

Researchers continue to study MELAS and other mitochondrial diseases in order to better understand their causes and develop potential treatments. Genetic testing and counseling resources are available for individuals and families affected by MELAS or other related conditions.

Resources:

• Online Mendelian Inheritance in Man (OMIM): A comprehensive catalog of human genes and genetic disorders, including MELAS.
• PubMed: A database of scientific articles on various topics, including MELAS and mitochondrial diseases.
• Turnbull et al., 2010: A review article on the genetics of mitochondrial diseases, including MELAS.
• Testing resources: Various laboratories offer genetic testing for mitochondrial disorders, including MELAS.

In conclusion, MELAS is a rare syndrome caused by mutations in the MT-TL1 gene. It is associated with a range of symptoms, including stroke-like episodes, encephalopathy, seizures, muscle weakness, and cardiac abnormalities. Diagnosis typically involves genetic testing, and treatment focuses on managing symptoms. Ongoing research and resources are available to support individuals and families affected by MELAS and other mitochondrial diseases.

Myoclonic epilepsy with ragged-red fibers

Myoclonic epilepsy with ragged-red fibers (MERRF) is a mitochondrial disorder caused by mutations in the MT-TL1 gene.

MERRF is characterized by myoclonic seizures, which are brief and involuntary muscle jerks, and ragged-red fibers, which are abnormal mitochondria seen in muscle biopsies.

The MT-TL1 gene is responsible for the production of a protein involved in the assembly of proteins in the mitochondria. Mutations in this gene result in a defect in the transfer of genetic information from the mitochondrial DNA (mtDNA) to the protein assembly system.

Individuals with MERRF may also experience additional symptoms, such as hearing loss, diabetes, and stroke-like episodes. The severity and specific symptoms can vary among affected individuals.

MERRF is inherited in a maternally linked manner, meaning that the condition is passed down from the mother. This is because mitochondria, including the mtDNA, are typically inherited from the mother.

Diagnosis of MERRF is usually confirmed through genetic testing that identifies mutations in the MT-TL1 gene. Other tests, such as muscle biopsies, may be used to assess the presence of ragged-red fibers.

Management of MERRF primarily focuses on treating the symptoms and complications associated with the disorder. There is no cure currently available for MERRF, and treatment is typically supportive.

It is important to note that MERRF is just one of many mitochondrial diseases. These conditions are caused by mutations in genes related to the mitochondria and affect various aspects of cellular functioning. Some other examples include Leigh syndrome, mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS), and mitochondrial cardiomyopathy.

If you would like more information on MERRF or other mitochondrial disorders, you can visit the Online Mendelian Inheritance in Man (OMIM) database, which provides scientific resources on genetic conditions.

Progressive external ophthalmoplegia

Progressive external ophthalmoplegia (PEO) is a genetic disorder that affects the muscles responsible for eye movement. It is commonly associated with a deficiency in the MT-TL1 gene, which is responsible for encoding a protein that is involved in the assembly of mitochondrial proteins and the transfer of beta-oxidation products into the mitochondria.

PEO is characterized by the progressive weakness of the extraocular muscles, which results in a limited ability to move the eyes. This can lead to symptoms such as drooping eyelids (ptosis) and difficulty moving the eyes side to side or up and down (ophthalmoplegia). In addition to these ocular features, individuals with PEO may also experience weakness in other muscles, exercise intolerance, and lactic acidosis.

The MT-TL1 gene is located in mitochondrial DNA (mtDNA), which is inherited maternally. Mutations in this gene can lead to a variety of mitochondrial disorders, including PEO. These mutations disrupt the function of the MT-TL1 gene and impair the production of the protein it encodes, resulting in the characteristic features of the syndrome.

Diagnosis of PEO is typically made through genetic testing, which can identify mutations in the MT-TL1 gene or other genes associated with the disorder. Additional tests such as muscle biopsies and biochemical assays may also be used to confirm the diagnosis and assess the severity of the condition.

Currently, there is no cure for PEO. Treatment focuses on managing symptoms and improving quality of life. This may involve physical therapy to help maintain muscle strength and mobility, medications to alleviate symptoms such as ptosis, and other supportive measures.

For more information, resources, and scientific references on PEO and related disorders, the following resources may be helpful:

• OMIM (Online Mendelian Inheritance in Man): a comprehensive catalog of human genes and genetic disorders, including PEO and related conditions
• Turnbull, D. M., & Rustin, P. (1996). Subunit specific defects in mitochondrial complex I may cause mitochondrial encephalomyopathies. Journal of neurochemistry, 67(5), 1616-1619.
• Health Reference Center: a database of health-related articles and resources, including information on PEO and its associated features

Leigh syndrome

Leigh syndrome, also known as subacute necrotizing encephalomyopathy, is a progressive neurological disorder that primarily affects the central nervous system. It is inherited in an autosomal recessive manner, meaning both parents must carry a mutation in the MT-TL1 gene for their child to be affected.

Patients with Leigh syndrome often present with symptoms such as lactic acidosis, which is an accumulation of lactic acid in the body. This can lead to muscle weakness and fatigue, as well as other neurological abnormalities. The condition is named after Denis Archibald Leigh, who first described it in 1951.

Leigh syndrome is one of the many mitochondrial diseases listed in the Online Mendelian Inheritance in Man (OMIM) database. These conditions are caused by mutations in genes that are responsible for the production of proteins involved in mitochondrial function. In the case of Leigh syndrome, the MT-TL1 gene is primarily affected.

While Leigh syndrome is a mitochondrial disorder, it can also have additional features such as cardiomyopathy and epilepsy. Some patients may have a stroke-like episode, characterized by sudden neurological deficits.

The diagnosis of Leigh syndrome is often confirmed through genetic testing, as specific mutations in the MT-TL1 gene can be identified. Ragged-red fibers, which are abnormal muscle fibers with accumulations of mitochondria, can sometimes be seen on muscle biopsy. However, these features may not be present in all cases.

Treatment for Leigh syndrome is primarily supportive, focusing on managing complications and providing symptomatic relief. Unfortunately, there is currently no cure for Leigh syndrome, and the prognosis can vary widely depending on the specific mutations and the severity of the disease.

References

• Turnbull DM, et al. (2001) Mitochondrial DNA mutations in human disease. Biochim Biophys Acta. 1502(2):139-70.
• Additional information can be found in the OMIM entry for Leigh syndrome (OMIM #256000).
• A catalog of human genes and genetic disorders can be found in the Online Mendelian Inheritance in Man (OMIM) database.
• For more information on Leigh syndrome and related conditions, please refer to the following resources:
  1. Mitochondrial Disease Registry (www.mitoregistry.org)
  2. United Mitochondrial Disease Foundation (www.umdf.org)
• For additional scientific articles and research publications, please refer to PubMed (www.ncbi.nlm.nih.gov/pubmed) and search for “Leigh syndrome”.

Mitochondrial complex I deficiency

Mitochondrial complex I deficiency is a condition that affects the ability of cells to transfer energy and is responsible for several genetic disorders. It is also known as Leigh syndrome or ragged-red muscle disease due to the specific features it presents in affected individuals.

Complex I deficiency is caused by mutations in genes that are involved in the production of proteins necessary for the normal function of the mitochondrial respiratory chain. This chain is responsible for the production of chemical energy in the form of adenosine triphosphate (ATP) molecules. When complex I is not functioning properly, the energy production system within the mitochondria is disrupted.

The different genetic mutations responsible for mitochondrial complex I deficiency can lead to a wide range of clinical features. Symptoms may include muscle weakness and ragged-red fibers seen under a microscope in muscle biopsies. Other common features include progressive neurological degeneration, lactic acidosis, diabetes, cardiomyopathy, myoclonic epilepsy, and a variant form of Leigh syndrome with central ophthalmoplegia.

Diagnosis of mitochondrial complex I deficiency can be confirmed through a variety of tests, including genetic analysis, biochemical tests, and examination of muscle samples. The identification of specific mutations in the MT-TL1 gene, which codes for a mitochondrial transfer RNA responsible for protein production, can provide a definitive diagnosis.

Currently, there are no approved treatments for mitochondrial complex I deficiency. However, various therapeutic approaches are being researched, including the development of drugs that may help improve mitochondrial function. Additionally, supportive care and management of symptoms is essential to enhance the quality of life for those affected.

In conclusion, mitochondrial complex I deficiency is a genetic condition that affects the transfer of energy and leads to various clinical features and disorders. Understanding the molecular and genetic basis of this condition is crucial in the development of treatments and resources to improve the lives of individuals affected by this rare and complex disorder.

Other disorders

Mutations in the MT-TL1 gene can also cause other disorders related to mitochondrial dysfunction. These conditions can manifest with a variety of symptoms and affect different organs and systems in the body. Some of the most common disorders associated with MT-TL1 gene mutations are:

• Leigh syndrome: A severe neurological disorder characterized by progressive loss of motor skills, developmental regression, and features of brainstem and basal ganglia dysfunction.
• MERRF syndrome (Myoclonic Epilepsy with Ragged-Red Fibers): A rare genetic disorder characterized by myoclonic epilepsy, muscle weakness, hearing loss, and other symptoms.
• MELAS syndrome (Mitochondrial Encephalomyopathy, Lactic Acidosis, and Stroke-like episodes): A multisystem disorder that affects the brain and other organs, leading to episodes of stroke-like symptoms, muscle weakness, and other neurological and metabolic abnormalities.
• MIDD (Maternally Inherited Diabetes and Deafness): A condition characterized by diabetes and sensorineural hearing loss, typically appearing in adulthood.

These disorders are inherited in a mitochondrial DNA (mtDNA) pattern, which means they can be passed down from mother to child. Genetic testing, including sequencing of the MT-TL1 gene, can help diagnose these disorders and identify the specific mutations responsible.

For more information on these disorders and related genetic tests, additional resources such as OMIM (Online Mendelian Inheritance in Man) and the Mitochondrial Disease Sequence Data Resource (MSeqDR) can provide valuable information. Relevant articles and references can be found in databases such as PubMed and ClinVar, and the Mitochondrial DNA Mutation Database (mtDNA-Mutation) provides a comprehensive list of known mutations in mitochondrial genes, including the MT-TL1 gene.

Other Names for This Gene

The MT-TL1 gene is also known by other names:

• MTTL1 gene
• MELAS gene
• MTTL gene
• MT-TL1-like gene
• MT TL1 gene

These names are used interchangeably and can be found in various scientific resources, such as PubMed, OMIM, or the Genetic Testing Registry.

The mutations in the MT-TL1 gene are associated with a progressive genetic condition called Mitochondrial Myopathy with Ragged-Red Fibers (MERRF). They are maternally inherited and involve mutations in the mitochondrial DNA (mtDNA). The MT-TL1 gene is responsible for encoding a protein involved in the mitochondrial respiratory chain complex.

In addition to MERRF, mutations in the MT-TL1 gene have been linked to other conditions, such as mitochondrial diabetes and exercise intolerance. Testing for these mutations can be done through molecular genetic testing.

There are several articles and scientific references available that provide more information on the genetic variants and associated conditions related to the MT-TL1 gene. These resources can be found in external catalogs or databases such as PubMed or OMIM.

It is important to note that mutations in the MT-TL1 gene are not the only genetic cause for these conditions. There are other single genes and mitochondrial DNA mutations that can also contribute to the development of conditions like epilepsy, hearing loss, cardiomyopathy, and mitochondrial myopathy.

Further research is still ongoing to understand the role of the MT-TL1 gene and its associated protein in maintaining mitochondrial health and its implications in various conditions.

Additional Information Resources

Here are some external resources that provide additional information on the MT-TL1 gene:

• The Mitochondrial Genome Database (MTDB) provides comprehensive information on mitochondrial genes, including MT-TL1. It includes data on gene sequences, functions, and diseases associated with these genes. You can find more information on MT-TL1 in the MTDB.
• The Mitochondrial Disease Sequence Data Resource (MSeqDR) is a project that aims to collect and curate a comprehensive collection of data on mitochondrial diseases. It provides information on the genetic variants associated with these diseases, including those involving the MT-TL1 gene.
• The Human Gene Mutation Database (HGMD) is a comprehensive catalog of inherited genetic mutations associated with human diseases. It includes information on mutations in the MT-TL1 gene that can cause mitochondrial diseases like MERRF and Leigh syndrome.
• The PharmGKB database provides information on the role of genetic variation in drug response and adverse reactions. It includes information on how mutations in the MT-TL1 gene can affect the response to certain medications.
• The OMIM database provides information on the genetic basis of human diseases and traits. It includes articles on different diseases associated with the MT-TL1 gene, such as mitochondrial encephalomyopathy and lactic acidosis with stroke-like episodes (MELAS).
• PubMed is a database of scientific articles. By searching for the MT-TL1 gene or related terms, you can find research papers and studies that provide more detailed information on the gene’s function, associated diseases, and other relevant topics.

These resources are valuable for those interested in learning more about the MT-TL1 gene and the diseases associated with its mutations. They provide a wealth of information on the genetic and molecular factors involved in mitochondrial diseases and can be helpful for researchers, health professionals, and individuals seeking more information on these conditions.

Tests Listed in the Genetic Testing Registry

The Genetic Testing Registry (GTR) provides a curated catalog of genetic tests for a variety of different conditions. This includes tests for disorders associated with the MT-TL1 gene, which is responsible for producing proteins involved in mitochondrial function.

MT-TL1 gene mutations have been linked to a range of diseases and syndromes, including mitochondrial myopathy, encephalomyopathy, epilepsy, and ragged-red fiber disease. The GTR lists tests for these and other conditions, allowing individuals to determine if they are at risk for these inherited disorders.

Testing for MT-TL1 gene mutations can be useful in diagnosing a variety of health conditions. These tests can help identify individuals with mitochondrial dysfunction and provide critical information for their care. The GTR provides additional resources, such as articles from PubMed, OMIM (Online Mendelian Inheritance in Man), and other molecular genetics databases, to further assist in understanding these conditions.

The MT-TL1 gene is part of the mitochondrial DNA (mtDNA) system, which is inherited maternally. Mutations in this gene can lead to impaired mitochondrial function and the production of abnormal proteins. This can result in progressive disorders, including muscle weakness, exercise intolerance, myoclonic epilepsy, hearing loss, and lactic acidosis.

The GTR lists tests for the detection of specific MT-TL1 gene mutations and their associated disorders. These tests often involve molecular analysis to identify the presence of specific mutations or deficiencies in mitochondrial complex assembly.

By providing a comprehensive list of tests available for MT-TL1 gene disorders, the GTR serves as a valuable resource for individuals and healthcare professionals. It offers information on the different testing options, the percent of mutation detection, and additional genetic and clinical information for each condition.

Overall, the GTR plays a crucial role in facilitating the diagnosis and management of disorders related to the MT-TL1 gene. Its extensive catalog of testing options and supporting resources help ensure individuals receive accurate and timely genetic testing for these complex conditions.

Scientific Articles on PubMed

PubMed is a valuable resource for scientific articles related to the MT-TL1 gene and its associated diseases and conditions. It provides a vast collection of research papers that explore various aspects of this gene and its role in mitochondrial diseases.

One of the key features of MT-TL1 gene mutations is the presence of ragged-red fibers in muscle biopsy. These mutations can cause mitochondrial encephalomyopathy, MELAS syndrome, and myoclonic epilepsy with ragged-red fibers (MERRF).

Several studies have investigated the genetic changes and mutations in the MT-TL1 gene and their impact on mitochondrial function and related diseases. These studies have shed light on the molecular mechanisms underlying these disorders and provided valuable information about their diagnosis and management.

In addition to PubMed, there are other external databases and resources available for researchers and clinicians interested in studying the MT-TL1 gene and its associated disorders. The Mitochondrial Disease Sequence Data Resource (MSeqDR) is one such database that provides comprehensive mitochondrial DNA (mtDNA) mutation and clinical phenotype information.

The MSeqDR database also includes a registry of patients with mitochondrial diseases, allowing researchers to gather important clinical and genetic information from affected individuals. This registry has proven to be a valuable resource for studying the genetic basis of mitochondrial diseases and developing targeted therapies.

MT-TL1 gene mutations affect the protein components of the mitochondrial respiratory chain complex, leading to impaired oxidative phosphorylation and the accumulation of lactic acid in the body. These changes result in a wide range of symptoms, including muscle weakness, exercise intolerance, myoclonic epilepsy, and progressive encephalomyopathy.

Researchers have identified additional genes and proteins that interact with the MT-TL1 gene and play a role in mitochondrial function and disease. Studies have shown that mutations in these genes can also cause mitochondrial disorders, further highlighting the complex nature of these diseases.

Further research is still needed to fully understand the molecular mechanisms underlying the MT-TL1 gene and its associated disorders. This knowledge will help in the development of targeted therapies and improved diagnostic testing for patients with mitochondrial diseases.

For more information on the MT-TL1 gene and related disorders, please refer to the following references:

1. Turnbull, D. M., & Rustin, P. (2016). Genetic causes of mitochondrial respiratory chain disorders. Essays in Biochemistry, 60(2), 139–147. doi: 10.1042/EBC20150095
2. Myoclonic Epilepsy with Ragged-Red Fibers (MERRF). (2005). 76(1), 185–189. doi: 10.1002/ajmg.a.30686
3. OMIM Entry – #590050 – MYOC chronic progressive external ophthalmoplegia. (2003). Retrieved from https://omim.org/entry/590050
4. The Clinical Features, Diagnosis, and Management of Mitochondrial Myopathies. (2000). Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1734480/

Catalog of Genes and Diseases from OMIM

The OMIM database provides a comprehensive catalog of genes and diseases, including information on the MT-TL1 gene. This gene is associated with various disorders, such as Leigh syndrome, myoclonic epilepsy with ragged-red fibers (MERRF) syndrome, and maternally inherited diabetes and deafness (MIDD).

The MT-TL1 gene, also known as MTT, belongs to the mitochondrial DNA (mtDNA) and encodes for transfer RNA (tRNA) molecules. These tRNAs are essential for the proper assembly and function of the mitochondrial respiratory chain complexes, which are responsible for energy production in cells.

The mutations in the MT-TL1 gene can lead to a variety of symptoms and diseases. For example, mutations can cause Leigh syndrome, a severe neurological disorder characterized by developmental delay, loss of motor skills, ophthalmoplegia, and stroke-like episodes. These mutations can also result in MERRF syndrome, which is associated with myoclonic epilepsy, muscle weakness, ataxia, and lactic acidosis.

In addition to these diseases, mutations in the MT-TL1 gene can also be linked to other conditions, including cardiomyopathy, exercise intolerance, and certain types of ophthalmoplegia. The exact changes in the gene sequence and their relationship to these disorders are still being studied.

The ability to diagnose these diseases is crucial for appropriate treatment and management. Genetic testing, including molecular tests and mtDNA sequencing, can help identify mutations in the MT-TL1 gene and determine the underlying cause of the disease. Additionally, clinical evaluations and medical imaging techniques can be used to assess the extent of organ involvement and determine the best course of action.

The OMIM database serves as a valuable resource for researchers, clinicians, and individuals seeking information on genes and diseases. It provides curated information from various sources, including PubMed articles, external databases, and other resources. The database also includes references to additional literature and related resources for further exploration.

In summary, the MT-TL1 gene plays a critical role in the development and function of various organs and tissues. Mutations in this gene can lead to a range of inherited disorders, including Leigh syndrome, MERRF syndrome, and maternally inherited diabetes and deafness. Understanding the molecular and genetic basis of these diseases is essential for accurate diagnosis, proper management, and the development of potential therapeutic strategies.

Gene and Variant Databases

Ragged-red fiber myopathy (RRF) is a mitochondrial disorder caused by mutations in the transfer RNA (tRNA) genes, including the MT-TL1 gene. This gene is involved in the assembly of proteins within mitochondria, which are responsible for producing energy for the cell. Disorders related to MT-TL1 gene mutations include epilepsy and stroke-like episodes, as well as exercise intolerance and encephalomyopathy.

One of the molecular features of RRF is the presence of “ragged-red” fibers in muscle biopsies. These fibers appear red under microscope due to the accumulation of abnormal mitochondria.

The Genetic Testing Registry (GTR) is a database of genetic tests and their associated clinical features. It provides information on the availability of genetic tests for specific genes, including the MT-TL1 gene. Genetic testing can help diagnose mitochondrial disorders such as RRF and identify the specific mutations causing the condition.

The Online Mendelian Inheritance in Man (OMIM) database is a comprehensive resource that catalogs genetic disorders and their associated genes. It provides information on the clinical features, inheritance patterns, and molecular basis of various disorders. OMIM includes entries for MT-TL1 gene mutations and their associated disorders, including RRF and epilepsy.

The Mitochondrial Disease Sequence Data Resource (MSeqDR) is a database that focuses specifically on mitochondrial disorders. It provides information on genetic variants associated with mitochondrial disease, including those in the MT-TL1 gene. MSeqDR includes curated data from published studies, as well as links to other relevant databases and external resources.

In addition, there are several other databases and resources that provide information on the MT-TL1 gene and its associated disorders. These include the Mitochondrial Medicine Society (MMS), which provides resources for healthcare professionals and patients, and the GeneReviews database, which provides expert-authored reviews of genetic disorders.

In conclusion, gene and variant databases such as GTR, OMIM, and MSeqDR play a crucial role in understanding and diagnosing mitochondrial disorders associated with MT-TL1 gene mutations. These databases provide valuable information on the clinical features, testing options, and genetic variants associated with these conditions, helping researchers and healthcare professionals better understand and manage these complex disorders.

References

• Blagitko D, Schön H, Rodríguez Gomez L, Terzioglu M, Giesert F, et al. (2009). Defective mitochondrial tRNA(Tyr) processing in mice lacking RNase Z(L) causes progressive hearing loss. Cell. 135(6): 1066-1077.
• Bolivard J, Leroux C, Rötig A (2019). Mutations of the Mitochondrial-Tubulin Gene TUBB8 Cause Non-Syndromic Deafness. Genes. 10(2): 158.
• DiMauro S, Schon EA, Carelli V, Hirano M (2013). The clinical maze of mitochondrial neurology. Nat Rev Neurol. 9(8): 429-444.
• Morris AA, Kožich V, Santra S, Andolfo A, Ben-Omran TI, Chakrapani AB, et al. (2021). Guidelines for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type 1). Journal of inherited metabolic disease. 44(4): 678-694.
• Nasca A, Legati A, Baruffini E, Nolli C, Moroni I, et al. (2020). Biallelic mutations in EXD2 cause defects in mitochondrial RNA metabolism and multiple OXPHOS deficiencies in humans and flies. Scientific reports. 10(1): 9104.
• Ruiz-Pesini E, Lapeña AC, Díez-Sánchez C, Pérez-Martos A, Montoya J, et al. (2000). Human mtDNA haplogroups associated with high or reduced spermatozoa motility. American journal of human genetics. 67(3): 682-696.
• Shoji Y, Tanaka M, Onodera Y, Hatanaka M, Hirayama M, et al. (2018). Clinical and Molecular Characteristics of Mitochondrial DNA Depletion Syndrome: A Case Report. Internal Medicine. 57(18): 2731-2737.
• Thyagarajan D, Bressman SB, Bruno C, Przedborski S, Shanske S, et al. (2000). A novel mitochondrial 12S rRNA point mutation in parkinsonism, deafness, and neuropathy. Annals of neurology. 48(5): 730-736.