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Test ID: MITOP Mitochondrial Full Genome Analysis by Next-Generation Sequencing (NGS)

Useful For

Diagnosis of the subset of mitochondrial diseases that results from mutations in the mitochondrial genome

 

A second-tier test for patients in whom previous targeted gene mutation analyses for specific mitochondrial disease-related genes were negative

 

Identifying mutations within genes of the mitochondrial genome that are known to be associated with mitochondrial disease, allowing for predictive testing of at-risk family members

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No

Testing Algorithm

If skin biopsy is received, fibroblast culture will be added and charged separately.

Method Name

Long-range polymerase chain reaction (LRPCR) followed by both Illumina and Ion Torrent next-generation sequencing (NGS)

Reporting Name

Mitochondrial Full Genome Analysis

Specimen Type

Varies


Shipping Instructions


Ambient blood is preferred to arrive within 96 hours of collection.



Necessary Information


Provide a reason for referral with each specimen. The laboratory will not reject testing if this information is not provided, but appropriate testing and interpretation may be compromised or delayed.



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call Mayo Medical Laboratories at 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube.

Specimen Stability Information: Ambient (preferred)/Refrigerated

 

Specimen Type: Cultured fibroblasts

Container/Tube: T-75 or T-25 flask

Specimen Volume: 1 full T-75 or 2 full T-25 flasks

Specimen Stability Information: Ambient (preferred)/Refrigerated <24 hours

 

Supplies: Fibroblast Biopsy Transport Media (T115)

Specimen Type: Skin biopsy

Container/Tube: Sterile container with any standard cell culture media (eg, minimal essential media, RPMI 1640). The solution should be supplemented with 1% penicillin and streptomycin. Tubes can be supplied upon request (Eagle's minimum essential medium with 1% penicillin and streptomycin [T115]).

Specimen Volume: 4-mm punch

Specimen Stability Information: Refrigerated (preferred)/Ambient

 

Supplies: Muscle Biopsy Kit (T541)

Specimen Type: Tissue biopsy

Collection Instructions: Prepare and transport specimen per instructions in Muscle Biopsy Specimen Preparation Sheet in Special Instructions.

Specimen Volume: 10-80mg

Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated

 

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Specimen Type: Blood spot

Preferred: Collection card (Whatman Protein Saver 903 Paper)

Acceptable: Ahlstrom 226 filter paper or Supplemental Newborn Screening Card (T493)

Specimen Volume: 2 to 5 Blood Spots on collection card

Collection Instructions:

1. An alternative blood collection option for a patient older than 1 year of age is finger stick.

2. Let blood dry on the filter paper at ambient temperature in a horizontal position for 3 hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry

Specimen Stability Information: Ambient (preferred)/Refrigerated

Additional Information:

1. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

2. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.


Specimen Minimum Volume

Blood: 1 mL
Tissue biopsy: 20 mg
Blood Spots: 5 punches-3 mm diameter

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Clinical Information

The mitochondrion occupies a unique position in eukaryotic biology. First, it is the site of energy metabolism, without which aerobic metabolism and life as we know it would not be possible. Second, it is the sole subcellular organelle that is composed of proteins derived from 2 genomes, mitochondrial and nuclear. A group of hereditary disorders due to mutations in either the mitochondrial genome or nuclear mitochondrial genes have been well characterized.

 

The diagnosis of mitochondrial disease can be particularly challenging as the presentation can occur at any age, involving virtually any organ system, and with widely varying severities. This test utilizes massively parallel sequencing, also termed next-generation sequencing (NGS) to determine the exact sequence of the entire 16,569 base-pair mitochondrial genome. The utility of this test is to assist in the diagnosis of the subset of mitochondrial diseases that result from mutations in the mitochondrial genome (mtDNA). This includes certain types of myopathies and neuro-opthalomologic diseases, such as mitochondrial encephalomyopathy, lactic acidosis, stroke-like episodes (MELAS), myoclonic epilepsy with ragged red fibers (MERRF), mitochondrial myopathy (MM), neurogenic muscle weakness, ataxia, retinitis pigmentosa (NARP), Leigh syndrome, Leber hereditary optic neuropathy (LHON), and chronic progressive external ophthalmoplegia (CPEO). In addition to the detection of single base changes with these disorders, large deletions, such as those associated with Kearns-Sayre or Pearson syndromes, are also detected. Mutations in mitochondrial proteins that are encoded by genes in the nucleus, such as the enzymes of fatty acid oxidation, are not detected using this test.

 

In contrast to mutations in nuclear genes, which are present in either 0, 1, or 2 copies, mitochondrial mutations can be present in any fraction of the total organelles, a phenomenon known as heteroplasmy. Typically, the severity of disease presentation is a function of the degree of heteroplasmy. Individuals with a higher fraction of mutant mitochondria present with more severe disease than those with lower percentages of mutant alleles. The sensitivity for the detection of mutant alleles in a background of wild-type (or normal) mitochondrial sequences by NGS is approximately 10%.

Reference Values

An interpretive report will be provided.

Interpretation

All detected alterations are evaluated according to American College of Medical Genetics and Genomics recommendations. 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 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.

Clinical Reference

1. Munnich A, Rotig A, Cormier-Daire V, Rustin P: Chapter 99: Clinical presentation of respiratory chain deficiency. In The Metabolic and Molecular Bases of Inherited Disease. Retrieved 2013 Available at Scriver's The Online Metabolic and Molecular Basis of Inherited Disease (OMBBID). Edited by D Valle, AL Beaudet, B Vogelstein, et al. McGraw-Hill Medical

2. Wallace DC, Lott MT, Brown MD, Kerstann K: Chapter 105: Mitochondria and neuro-ophthalmologic diseases. In The Metabolic and Molecular Bases of Inherited Disease. Retrieved 2013

Available at Scriver's The Online Metabolic and Molecular Basis of Inherited Disease (OMBBID). Edited by D Valle, AL Beaudet, B Vogelstein, et al. McGraw-Hill Medical

3. Wong LJ: Molecular genetics of mitochondrial disorders. Dev Disabil Res Rev 2010 Jun;16(2):154-162

Day(s) and Time(s) Performed

Monday through Friday; Varies

Analytic Time

8 weeks

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

Mitochondrial Full Genome Analysis

81460 

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MITOP Mitochondrial Full Genome Analysis In Process

 

Result ID Test Result Name Result LOINC Value
55281 Result Summary 50397-9
55282 Result In Process
55283 Interpretation In Process
55284 Additional Information 48767-8
55285 Specimen 31208-2
55286 Source 31208-2
55287 Released By No LOINC Needed

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Molecular Genetics: Biochemical Disorders Patient Information (T527) in Special Instructions

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen (http://www.mayomedicallaboratories.com/it-mmfiles/neurology-request-form.pdf)

Mayo Medical Laboratories | Genetics and Pharmacogenomics Catalog Additional Information:

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