mtDNA, MELAS, Myoclonic Epilepsy with Ragged Red Fibers, MERRF, Neurogenic Muscle Weakness, Ataxia, and Retinitis Pigmentosa, NARP, Leigh syndrome, LHON, Chronic progressive external ophthalmoplegia, CPEO, Pearson syndrome, Next Gen Sequencing Test, Leber's hereditary optic neuropathy, Kearns-Sayre syndrome
For skin biopsy or cultured fibroblast specimens, fibroblast culture testing will be performed at an additional charge. If viable cells are not obtained, the client will be notified.
Diagnosis of the subset of mitochondrial diseases that results from variants in the mitochondrial genome
A second-tier test for patients in whom previous targeted gene variant analyses for specific mitochondrial disease-related genes were negative
Identifying variants within genes of the mitochondrial genome that are known to be associated with mitochondrial disease, allowing for predictive testing of at-risk family members
This test includes amplification of the entire mitochondrial genome by long-range polymerase chain reaction (LR-PCR) followed by sequencing on the next-generation sequencing (NGS) platform to evaluate for variants within the mitochondrial genome.
Next-generation sequencing (NGS) is used to test for the presence of variants, including: 13 protein coding genes, 22 transfer RNA genes, and 2 ribosomal RNA genes, within the mitochondrial genome
Large deletions within the mitochondrial genome and their locations are determined from the NGS data.
This assay is only useful for detecting mitochondrial genomic variants. Depletion of mitochondrial DNA levels or variants in mitochondrial genes encoded by the nuclear genome is not within the scope of this assay.
Ambient blood is preferred to arrive at Mayo Labs within 96 hours of collection.
Molecular Genetics: Biochemical Disorders Patient Information (T527) is available to provide information useful for accurate test interpretation. At minimum, provide a reason for testing with each specimen. Although testing may proceed without this information, ordering providers are strongly encouraged to complete the form and send it with the specimen.
Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.
A small percentage of individuals who have mitochondrial genome involvement may have a variant that is not identified by the methods performed. The absence of a variant, therefore, does not eliminate the possibility of a mitochondrial disease due to variant in the mitochondrial genome. Variants in mitochondrial genes encoded by the nuclear genome will not be detected with this assay. For predictive testing of asymptomatic individuals, it is important to first document the presence of a gene variant in an affected family member.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Misinterpretation of results may occur if the information provided is inaccurate or incomplete.
In some cases, DNA variants of undetermined significance may be identified.
Rare alterations exist that could lead to false-negative or false-positive results. If results obtained do not match the clinical findings, additional testing should be considered.
Multiple in-silico evaluation tools were used to assist in the interpretation of these results. These tools are updated regularly; therefore, changes to these algorithms may result in different predictions for a given alteration. Additionally, the predictability of these tools for the determination of pathogenicity is currently unvalidated.
Unless reported or predicted to cause disease, alterations in protein coding genes that do not result in an amino acid substitution are not reported. The mitochondrial haplogroup classification of the patient will be reported, but the individual nucleotide changes that define the haplogroup will not be reported. These and common alterations identified for this patient are available upon request.
Reclassification of Variants-Policy:
At this time, it is not standard practice for the laboratory to systematically review likely deleterious alterations or variants of uncertain significance that are detected and reported. The laboratory encourages health care providers to contact the laboratory at any time to learn how the status of a particular variant may have changed over time.
All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance. The degree of heteroplasmy of each single nucleotide or INDEL (insertion/deletion) variant, defined as the ratio (percentage) of variant sequence reads to the total number of reads, will also be reported. Large deletions will be reported as either homoplasmic or heteroplasmic, but the degree of heteroplasmy will not be estimated, due to possible preferential amplification of the smaller deletion product by long-range PCR.