AUTOSOMAL DOMINANT PROGRESSIVE EXTERNAL OPTHALMOPLEGIA (ad-PEO) WITH mtDNA DELETIONS
POLG2 Sequencing
MITOCHONDRIAL DNA ANALYSIS
Also known as: PEOA4

Description:

The replication and maintenance of mitochondrial DNA is dependent upon DNA polymerase gamma, the only DNA polymerase in mitochondrial matrix. DNA polymerase gamma consists of a 140-kD catalytic subunit (POLG1) and two 55-kD accessory subunits (POLG2) to form a heterotrimer holoenzyme. While mutations in POLG1 (test number 3065) have been found to be associated with PEO (test number 3300), SANDO, Parkinsonism, and Alpers syndrome, only one heterozygous mutation in POLG2 is currently reported to be associated with PEO (OMIM#610131). The in vitro study showed that in the presence of the POLG2 mutation the holoenzyme showed reduced DNA binding affinity. Thus, the disease in the reported patient is most likely due to haploinsufficiency or heterodimerization of the mutant and wild proteins. The human POLG2 gene is mapped to chromosome 17q23-q24. It contains 8 exons encoding a protein of 485 amino acids.

Reasons for Referral:

Confirmation of a clinical diagnosis
Carrier testing

Testing Methodology:

The exons and flanking intronic regions of the POLG2 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

Turnaround Time:

2-4 weeks

CPT Codes and Prices:

Index: 83891, 83904x16, 83898x8, 83912, 83894x2
Known Familial Mutation: 83904x4, 83898x2, 83912, 83891, 83894x2

References:

1. Longley MJ, Clark S, Yu Wai Man C, Hudson G, Durham SE, Taylor RW, Nightingale S, Turnbull DM, Copeland WC, Chinnery PF. (2006) Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. Am J Hum Genet 78: 1026-34
2. Yakubovskaya E , Chen Z , Carrodeguas JA , Kisker C, Bogenhagen DF. (2006) J Biol Chem 281:374-82

Shipping Information

Forms:

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

Test Codes:

Index: 3380
Known Familial Mutation: 3381