OPTIC ATROPHY TYPE 1
OPA1 Gene Sequencing
MITOCHONDRIAL DNA ANALYSIS

Description:

Optic atrophy type 1 (OPA1, MIM 165500) is a dominantly inherited optic atrophy or progressive ophthalmologic disorder. It is characterized by an insidious onset of visual impairment in early childhood with moderate to severe loss of visual acuity, temporal optic disc pallor, color vision deficits, and centrocecal scotoma of variable density Two-thirds of the autosomal dominant optic atrophy cases are caused by a mutation in the OPA1 gene. OPA1 is a major organizer of the mitochondrial inner membrane and is required for the maintenance of cristae integrity. As the loss of OPA1 committed cells to apoptosis without any other stimulus, OPA1 is involved in the sequestration of cytochrome c, and may be a target for mitochondrial apoptotic effectors. OPA1 gene comprises 30 coding exons and spans more than 69 kb of genomic sequence. OPA1 has 8 mRNA isoforms as a result of the alternative splicing of exon 4 and 2 novel exons designated 4b and 5b. OPA1 gene is mapped to 3q28-q29. To date, over 100 OPA1 mutations were identified according to online OPA1 mutation database.

Reasons for Referral:

Confirmation of a clinical diagnosis
Carrier testing
Prenatal diagnosis for known familial mutations

Testing Methodology:

The exons and flanking intronic regions of the OPA1 gene are PCR amplified and sequenced in both the forward and reverse directions.

Specimen Requirements:

Blood: EDTA (purple-top) tubes: Adult: 14 cc; Child: 6 cc; Infant: 2-3 cc.
Requisition form must accompany the specimen. To receive forms, additional information or specimen collection kits, please contact the laboratory. Please call laboratory for specific requirements for prenatal testing.

Turnaround Time:

Index: 4 weeks
Known Familial Mutation: 2 weeks

CPT Codes and Prices:

Index: 83891, 83904x60, 83898x30, 83912, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

Shipping Information

Forms:

>> Gene Sequencing Requisition or Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included
>> Prenatal Requisition

References:

1. Delettre, C, Griffoin, JM, Kaplan, J. et al. Mutation spectrum and splicing variants in the OPA1 gene. Hum Genet. 2001; 109 :584–591.
2. Ferraris S, Clark S, Garelli E, et al. Progressive External Ophthalmoplegia and Vision and Hearing Loss in a Patient With Mutations in POLG2 and OPA1 . Arch Neurol. 2008; 65(1):125-131.
3. Merkwirth C, Dargazanli S, Tatsuta T, et al. Prohibitins control cell proliferation and apoptosis by regulating OPA1-dependent cristae morphogenesis in mitochondria. Genes & Dev. 2008 22: 476-488.

Test Code:

Index: 3465
Known Familial Mutation: 3466
Prenatal: 3467