AUTOSOMAL DOMINANT PROGRESSIVE EXTERNAL OPTHALMOPLEGIA (ad-PEO) WITH mtDNA DELETIONS

POLG2 Sequencing

MITOCHONDRIAL DNA ANALYSIS

Also known as: PEOA4


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
  • Prenatal diagnosis for known familial mutations

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
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:

2-4 weeks

CPT Codes and Prices:

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

Shipping Information


Forms:

>> Mitochondrial Requisition - Mitochondrial Diagnostic Checklist is included

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.

Test Codes:

Index: 3380
Known Familial Mutation: 3381
Prenatal: 3382

Medical Genetics Laboratories
Baylor College of Medicine · Houston, TX 77030
Phone: 1-800-411-GENE · Fax: 713-798-2787
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