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HelpTest ID: MITON Mitochondrial Nuclear Gene Panel by Next-Generation Sequencing (NGS), Varies
Useful For
Diagnosis of the subset of mitochondrial disease that results from variants in the nuclear-encoded genes
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 nuclear 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 |
|---|---|---|---|
| FIBR | Fibroblast Culture | Yes | No |
| CRYOB | Cryopreserve for Biochem Studies | No | No |
Testing Algorithm
If skin biopsy is received, fibroblast culture and cryopreservation for biochemical studies will be added at an additional charge.
See Neuromuscular Myopathy Testing Algorithm in Special Instructions.
Special Instructions
Method Name
Custom Sequence Capture and Targeted Next-Generation Sequencing (NGS) followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing when appropriate
Reporting Name
Mitochondrial Nuclear Gene PanelSpecimen Type
VariesShipping Instructions
Specimen preferred to arrive within 96 hours of collection.
Necessary Information
Specimen Required
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.
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.
3. To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.
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
Specimen Type: Skin biopsy
Supplies: Fibroblast Biopsy Transport Media (T115)
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.
Specimen Volume: 4-mm punch
Specimen Stability Information: Refrigerated (preferred)/Ambient
Specimen Type: Tissue biopsy
Supplies: Muscle Biopsy Kit (T541)
Collection Instructions: Prepare and transport specimen per instructions in Muscle Biopsy Specimen Preparation in Special Instructions.
Specimen Volume: 10-80 mg
Specimen Stability Information: Frozen (preferred)/Ambient/Refrigerated
Specimen Minimum Volume
Blood: 1 mL
Tissue Biopsy: 200 mg
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
The mitochondrion occupies a unique position in eukaryotic biology. It is the site of energy metabolism, and 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 variants in either the mitochondrial genome or nuclear mitochondrial genes has been well characterized.
The diagnosis of mitochondrial disease can be particularly challenging as the presentation can occur at any age, involve virtually any organ system, and be associated with widely varying severities. Due to the considerable overlap in the clinical phenotypes of various mitochondrial disorders, it is often difficult to distinguish these specific inherited disorders without genetic testing. This test utilizes massively parallel sequencing, also termed next-generation sequencing (NGS), to analyze 176 nuclear-encoded genes implicated in mitochondrial disease. The utility of this test is to assist in the diagnosis of the subset of mitochondrial diseases that result from variants in the nuclear encoded genes. This includes disorders of mitochondrial protein synthesis, disorders of coenzyme Q10 biosynthesis, disorders of the respiratory chain complexes and disorders of mtDNA maintenance (ie, mitochondrial DNA depletion disorders).
See Targeted Genes Interrogated by Mitochondrial Nuclear Gene Panel in Special Instructions for details regarding the targeted genes identified by this test.
Reference Values
An interpretive report will be provided.
Interpretation
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.
Clinical Reference
1. Richards CS, Nazneen A, Bale S, et al: Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015 May;17(5):405-424
2. Munnich A, Rotig A, Cormier-Daire V, Rustin P: Clinical presentation of respiratory chain deficiency. In: Valle D, Antonarakis S, Ballabio A, Beaudet AL, Mitchell GA, eds. The Metabolic and Molecular Basis of Inherited Disease. McGraw-Hill Education; 2019. Accessed September 28, 2020. https://ommbid.mhmedical.com/content.aspx?bookid=2709§ionid=225086827
3. Wong LJ: Molecular genetics of mitochondrial disorders. Dev Disabil Res. Rev 2010 Jun;16(2):154-162
Day(s) Performed
Varies
Report Available
8 to 10 weeksTest 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 US Food and Drug Administration.CPT Code Information
81440
88233-Tissue culture, skin or solid tissue biopsy (if appropriate)
88240-Cryopreservation (if appropriate)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| MITON | Mitochondrial Nuclear Gene Panel | In Process |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 40220 | Result Summary | 50397-9 |
| 40221 | Result | 82939-0 |
| 40222 | Interpretation | 69047-9 |
| 40223 | Additional Information | 48767-8 |
| 40224 | Specimen | 31208-2 |
| 40225 | Source | 31208-2 |
| 40226 | Released By | 18771-6 |
Forms
1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available in Special Instructions:
-Informed Consent for Genetic Testing (T576)
-Informed Consent for Genetic Testing-Spanish (T826)
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.
mml-neurometabolic, mml-neuromuscular, mml-pediatric, mml-movement-disorders