NGS Mitochondrial Depletion Panel

 

Disorders

NGS Mitochondrial Depletion Panel

Gene Names
ABAT GFER POLG SUCLG1
AGK MFN2 POLG2 TFAM
APTX MGME1 RRM2B TK2
DGUOK MPV17 SLC25A4 TWNK
DNA2 OPA1 SPG7 TYMP
FBXL4 OPA3 SUCLA2  
Clinical info

This panel consists of 23 nuclear-encoded genes that have been associated with mitochondrial DNA depletion disorders. These nuclear genes are responsible for the maintenance of mitochondrial DNA, so dysfunction of this process can lead to multisystem involvement and tend to be progressive. Variants of these disorders include encephalomyopathic, myopathic, hepatocerebral, and neurogastrointestinal types. Common symptoms may include the following: muscle weakness/hypotonia; motor and developmental delays in early-onset cases; digestive problems such as IBS, diarrhea, and constipation or other dysmotility; neurological issues such as migraines, seizures, and strokes; dysautonomia; kidney disease, cardiomyopathy; liver disease; vision problems, especially ophthalmoplegia, and hearing loss; and fatigue. While the majority of nuclear mitochondrial disorders are inherited in an autosomal recessive pattern, some conditions demonstrate autosomal dominant inheritance. These conditions can occur in infancy or early childhood and typically have a poor prognosis. However, tremendous clinical variability exists among these disorders. 

List of Genes and Conditions

Indications

Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Detection

The current design of the Neuromuscular disorders panel covers the coding region for all 23 genes and the flanking intronic sequences. This method allows for analysis of greater than 98% of the targeted sequence for the detection of nucleotide substitutions and small deletions and duplications. Large deletions and duplications will not be detected by this panel. Mutations and variants identified on the panel are confirmed with Sanger sequencing. All novel and apparently pathogenic changes are reported when found within the coding region as well as within 10 basepairs of each intron/exon boundary for each gene. Promoter and 3' untranslated sequences are not included in the current analysis. It should be noted that the current protocol is not specifically designed to detect copy number alterations and single exon deletions may require additional follow-up to determine whether or not they represent technical artifacts.

We recommend further array-based testing to more accurately address the concerns of dosage alterations. The Cytogenetic Laboratory at GGC offers a high resolution whole genome SNP microarray. The GGC Diagnostic Laboratory Directors are available for further consultation regarding the limitations of the NGS and array testing procedures.

Associated Tests

Effective January 1, 2017, all NGS panels are performed on an exome backbone with the potential for reflex to whole exome sequencing at a reduced cost. Please contact the laboratory to discuss the requirements for exome sequencing.

Specimen Requirements 5 to 10 ml of peripheral blood collected in an EDTA (lavender top) Vacutainer tube is preferred. The minimal blood needed for reliable DNA isolation is 3 ml.
Transport The specimen should be kept at room temperature and delivered via overnight shipping. FedEx is preferred. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen.  Samples collected on Friday can be safely designated for Monday delivery.
Turnaround time 8-10 weeks
Prenatal testing

If the pathogenic mutation(s) are identified in an affected individual using this panel, prenatal diagnosis is available for future pregnancies. Sanger sequencing will be used for prenatal diagnosis when there is a known familial mutation. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.

CPT Codes 81479
Cost $3,500

Insurance billing is available for this test. The Billing Form is required along with copies of the authorization or letter of agreement from the insurance company.
Contact For further information contact one of our This email address is being protected from spambots. You need JavaScript enabled to view it. at 1-800-473-9411.

NGS Panel Requisition Form

Please submit a completed Requisition Form with all samples.

 

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Molecular Diagnostic Lab Faculty

Clearing Div - do not delete (is not shown)