Ad-PEO-2 AUTOSOMAL DOMINANT PROG

Ad-PEO-2 AUTOSOMAL DOMINANT PROGRESSIVE EXTERNAL OPTHALMOPLEGIA 2

DESCRIPTION - Nuclear Mitochondrial DNA Analysis

The most abundant mitochondrial protein is the ADP/ATP adenine nucleotide translocator (ANT). In its functional state, it is a homodimer of 30-kD subunits embedded asymmetrically in the inner mitochondrial membrane. The dimer forms a gated pore through which ADP is moved from the matrix into the cytoplasm. Dominant missense mutations in the heart and skeletal muscle-specific isoform of the ANT1 gene cause autosomal dominant progressive external ophthalmoplegia (ad-PEO). Affected patients accumulate multiple mitochondrial DNA deletions in muscle. Recently, autosomal recessive ANT1 mutations have been identified in patients with hypertrophic cardiomyopathy, mild myopathy with exercise intolerance and lactic acidosis but no ophthalmoplegia. ANT1 is a mitochondrial solute carrier SLC25A4. The ANT1 gene contains 4 exons and is located on chromosome 4q35.

Related Tests: Ad-PEO PANEL-SEQGX, TWINKLE-SEQGX

Test Order Code	ANT1-SEQGX
CPT Codes	83891 x 1, 83898 x 4, 83904 x 8, 83912 x 1
Indications For Testing	Clinical diagnosis of hypertrophic cardiomyopathy Mild myopathy with exercise intolerance and lactic acidosis Confirmation of a clinical diagnosis Assistance with a clinical diagnosis Prenatal diagnosis only if a familial mutation is identified Genetic counseling
Turn Around Time	Up to 2 weeks. Expedited analysis is available upon request for an additional charge.
Specimen Requirements	Peripheral Blood All peripheral blood collections require Purple/Lavender-top (EDTA) vaccutainer tubes. Adults: 2 tubes each with 7.5 mL whole blood Children & Infants: 1 tube of 5-6 mL whole blood Keep samples at ambient temperature and ship by overnight courier to arrive at the Molecular Laboratory within 24 hrs after collection of the specimen. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature.
Specimen Kits	DNA Specimen Collection Kits can be obtained from Transgenomic Molecular Laboratory.
Shipping and Contact Information	Transgenomic Molecular Laboratory 12325 Emmet Street Omaha, NE 68164 USA Phone: (866) 500-GENE / (866) 500-4363 Fax: (402) 452-5447 E-mail: labservice@transgenomiclabs.com
Test Submission and Patient Consent Forms	Test Requisition Form Patient Consent Form Due to the unique nature of genetic testing, patients should receive pre-test and post-test counseling. Informed consent is recommended.
Test Methodology	The exons and flanking intron regions of ANT1 gene are PCR amplified and bidirectional sequencing is performed.
Sensitivity	Accuracy – 99% accuracy reported for mutation detection with bidirectional sequencing analysis. Limitations - The methodology will detect mutations located only within the regions defined by the primers. Some sequence alterations detected by this assay will be of unknown clinical relevance. Interpretation of test results should be in the context of the patient’s clinical and family histories, ethnicity, and other laboratory test results.
References	Palmieri L et al. (2005) Complete loss-of-function of the heart/muscle-specific adenine nucleotide translocator is associated with mitochondrial myopathy and cardiomyopathy. Hum. Mol. Genet. 14: 3079-3088. Agostino A et al. (2003) Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology 60: 1354-1356. Napoli L et al. (2001) A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family. Neurology 57: 2295-2298.

OMIM Entries for:

Progressive External Ophthalmoplegia with Mitochondrial DNA Deletions, Autosomal Dominant

103220	SOLUTE CARRIER FAMILY 25(MITOCHONDRIAL CARRIER), MEMBER 4; SLC25A4
609283	PROGRESSIVE EXTERNAL OPHTHALMOPLEGIA WITH MITOCHONDRIAL DNA DELETIONS, AUTOSOMAL DOMINANT, 2

Additional References

Mitomap
A human mitochondrial genome database. A compendium of polymorphisms and mutations of the human mitochondrial DNA. http://www.mitomap.org/

Note: The performance characteristics of this test were validated by TRANSGENOMIC Molecular Laboratory. The U.S. Food and Drug Administration (FDA) has not approved this test. However, FDA approval is currently not required for clinical use of this test. The results are not intended to be used as the sole means for clinical diagnosis or patient management decisions. TRANSGENOMIC Molecular Laboratory is authorized under Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity testing.