mtSEEK®

by Courtagen Life Sciences, Inc.

mtSEEK® Mitochondrial Genome Sequencing with Deletion Detection and Heteroplasmy Analysis

Courtagen’s mtSEEK®test provides sequence analysis, deletion detection and heteroplasmy analysis for the 16,569 bases that make up the 37 genes of the mitochondrial genome.

(See also Courtagen’s nucSEEK®test which uses next generation sequencing to detect variants in over 1,100 nuclear genes associated with mitochondrial function.)

What is Mitochondrial Disorders?

Mitochondrial disorders occur in approximately 1 of every 4,000 individuals. Such disorders result from failures of the mitochondria, which are specialized organelles in the cell that act as the energy source for daily body activity. When mitochondria fail, less and less energy is generated within the cell. As a result, whole systems begin to fail, and the health of the person in whom this is happening is severely compromised. The disease primarily affects children, but can affect adults as well.

What are the symptoms of Mitochondrial Disorders?

Diseases of the mitochondria cause the most damage to cells of high energy demand such as the brain, heart, liver, skeletal muscles, kidneys, and the endocrine, gastrointestinal, and respiratory systems.

The type of disease that shows up as a result of mitochondrial dysfunction can vary from person to person, even within the same family. It often involves several body systems at once, and symptoms can be intermittent.

There are multiple medical conditions and clinical problems that can be affected by mitochondrial dysfunction. Examples include, but are not limited to: developmental delays, autism spectrum disorders, seizures, migraines, muscle weakness, chronic fatigue, complex regional pain syndrome, and autonomic dysfunction (including cyclic vomiting syndrome).

What are the Benefits of Genetic Testing for Mitochondrial Disorders

Making a molecular diagnosis of mitochondrial disease requires the identification of DNA abnormalities (both mitochondrial and nuclear) that are known to cause disease.
Variants in mitochondrial DNA are maternally inherited and cause a variety of known mitochondrial diseases. Courtagen’s mtSEEK® test sequences all 16,569 bases making up the 37 genes of the mitochondrial genome. The assay also provides highly sensitive detection of heteroplasmy levels as low as 2.5%.

Courtagen’s nucSEEK® test identifies variants in over 1,000 nuclear genes associated with mitochondrial function.  Nuclear genes are increasingly being identified as significant factors in mitochondrial disorders.

A positive result provides a molecular diagnosis for what is otherwise typically a long and complex diagnostic work up.

  • A genetic diagnosis provides knowledge about the progression of disease
  • Identified genetic variants may guide targeted therapy
  • Test results may determine whether other family members should be tested.

What is the unique advantage of mtSEEK® test from Courtagen?

Courtagen’s proprietary DREAM PCR process ensures superior lab decontamination and long sequencing reads result in exceptional coverage and sensitivity for the target genes in each panel. Courtagen’s high quality coverage exceeds that of shorter sequencing read tests and lower coverage whole exome sequencing (WES) approaches.

Courtagen’s Clinical Team has over 25 years of experience in treatment and genetic interpretation of neurological disorders, and results are delivered in a concise clinical report to help determine diagnosis and assist with decisions about treatment and disease management.

 mtSEEK® FAQs

[accordion][accordion-item title="How do I order a test?"]Please contact us and let us know if you would like to order a test for a patient. One of our representatives will get in touch with you and advise on the workflow, and provide the necessary forms and sample collection kits. Once the samples have been collected, we will coordinate the shipment of the sample to the laboratory. Once testing is completed, the report will be sent to you.[/accordion-item][accordion-item title="How is mtSEEK® performed?"]The mtDNA is amplified using long range PCR, enabling the most sensitive detection of deletions and duplications in the mitochondrial genome. Next generation sequencing is performed with 250bp paired-end reads – providing highly accurate mapping and assembly, and avoiding nuclear mtDNA (numt) mismapping. Barcode embedded process controls are run concurrently with every patient sample. The use of these controls and deep sequencing coverage achieves maximum sensitivity for heteroplasmy detection.[/accordion-item][accordion-item title="How long does it take for a mtSEEK® result?"]4-6 weeks[/accordion-item][accordion-item title="What does a mtSEEK® result reveal to a patient?"]The report result is based on the significance of the combination of variants identified in the individual’s test result. Courtagen’s bioinformatics and clinical teams complete an analysis of the mitochondrial genome sequence, including deletion and heteroplasmy analysis. Genetic variants may be classified as positive (known disease causing mutation associated with epilepsy), negative (no disease causing mutations identified), or variant of unknown significance (VUS). A VUS indicates that a genetic variant was identified, but information is insufficient, and it is unclear if the variant has clinical significance. Additional testing of family members may be requested for further interpretation. Often mtDNA variants are only present in a fraction of a cell’s mitochondrial DNA (mtDNA), whereas the remaining mtDNA has a normal sequence. This condition is called heteroplasmy. The percent heteroplasmy reported is the percentage of abnormal mtDNA identified. A positive result provides a molecular diagnosis for what is otherwise typically a long and complex diagnostic work up.

  • A genetic diagnosis provides knowledge about the progression of disease
  • Identified genetic variants may guide targeted therapy
  • Test results may determine whether other family members should be tested.

(See also Courtagen’s nucSEEK® test which uses next generation sequencing to detect variants in over 1,100 nuclear genes associated with mitochondrial function.)[/accordion-item][accordion-item title="What symptoms/syndromes indicate that a patient is suitable for the mtSEEK® test?"]Genetic variants in mtDNA are maternally inherited. Common symptoms include:

  • Seizures and other neurological problems
  • Autism spectrum disorders, autistic-like features
  • Developmental delays, learning disabilities
  • Dementia
  • Migraines
  • Heart, liver or kidney disease
  • Visual and/or hearing problems
  • Muscle weakness, poor muscle coordination
  • Poor growth, failure to thrive
  • Delayed gastric emptying
  • Chronic diarrhea or constipation
  • Cyclic vomiting
  • Diabetes
  • Thyroid and/or adrenal dysfunction

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