OPA1
|
 |
DESCRIPTION - Nuclear Mitochondrial DNA Analysis
Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Optic atrophy type 1 (OPA1, or Kjer type optic atrophy) is characterized by bilateral and symmetric optic nerve pallor associated with insidious decrease in visual acuity usually between ages four and six years, visual field defects, and color vision defects. Visual impairment is usually moderate (6/10 to 2/10), but ranges from mild or even insignificant to severe (legal blindness with acuity <1/20). The visual field defect is typically centrocecal, central, or paracentral; it is often large in those with severe disease. The color vision defect is often described as acquired blue-yellow loss (tritanopia). Other findings can include auditory neuropathy resulting in sensorineural hearing loss that ranges from severe and congenital to subclinical (i.e., identified by specific audiologic testing only).
Normal gene product: The OPA1 gene codes for Dynamin-like 120 kd Protein - a mitochondrial dynamin-related GTP protein of 960 amino acids and maps to chromosome 3 at loci 3q28-q29. It has 31 exons but the last one is not coded. OPA1 has 8 mRNA isoforms as a result of the alternative splicing of exon 4 and 2 novel exons designated 4b and 5b. This is the first dynamin-related protein found to be involved in human disease. OPA1 appears to exert its function in mitochondrial biogenesis and stabilization of mitochondrial membrane integrity that may affect multiple organ systems adding complexity to diagnosis. Likewise, Dominant Optic Atrophies are also due to mutations in the OPA1 gene in about 60-70% of cases and OPA1 mutations may be associated with additional phenotypes with neuromuscular involvement, including sensorineural deafness, cerebellar ataxia, axonal sensory-motor polyneuropathy and mitochondrial myopathy frequently complicated by CPEO. Because of the complexity of phenotypes associated with disease, a Mitochondrial Whole Genome Analysis should be considered as part of the testing process.
Related Tests: MTDNA-LHON , MITO-WGA
| Test Order Code | OPA1 |
| CPT Codes |
83891 x 1, 83898 x 9, 83904 x 18 |
| Indications For Testing |
|
| Turn Around Time | Less than three weeks. Expedited analysis is available upon request for an additional charge. |
| Specimen Requirements |
Ship one of the following:
Saliva
Peripheral Blood |
| Specimen Kits | DNA Specimen Collection Kits can be obtained from Transgenomic Labs. |
| Shipping and Contact Information |
Transgenomic Labs Five Science Park, New Haven, CT 06511 USA Phone:1.877.274.9432 Fax: 203.786.3418 E-mail: labservice@transgenomiclabs.com |
| Test Submission and Patient Consent Forms |
Test Requisition and 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 | DNA is prepared from blood and exons 1-30 of the OPA1 gene are amplified by PCR. The subsequent amplicons are scanned for mutations on the WAVE® System using SURVEYOR® Nuclease heteroduplex analysis. Mutations are identified by double-stranded DNA sequencing. |
| References |
|
OMIM Entries for:
OPA1, Optic Atrophy Type 1
| 605290 | OPA1 GENE; OPA1 |
| 165500 | OPTIC ATROPHY 1; OPA1 |
| 125250 | OPTIC ATROPHY 1 AND DEAFNESS OPTIC ATROPHY, DEAFNESS, OPHTHALMOPLEGIA, AND MYOPATHY, INCLUDED |
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 Labs. 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 Labs is authorized under Clinical Laboratory Improvement Amendments (CLIA) to perform high-complexity testing.