Sign in →

Test Code LAB1889 POLG Sequencing

Clinical System Name

Polymerase Gamma (POLG) Sequencing

Description

Mutations in the gene encoding polymerase gamma, POLG (formerly POLG1), cause mtDNA depletion or multiple mtDNA deletions resulting in a highly heterogeneous group of mitochondrial diseases.

 

POLG full gene sequencing is appropriate for individuals with any of the following:

  • Progressive external opthalmoplegia
  • Cerebellar ataxia ± seizures
  • Acute liver failure
  • Multiple mtDNA deletions or mtDNA depletion in affected tissues
  • Cytochrome oxidase (COX)-deficient muscle fibers

 

Also available: Targeted Gene Variant Sequencing (LAB1915) - For targeted analysis of variants previously identified through clinical testing of a family member or research testing of the individual.  Please review requirements and restrictions for testing.

Sample Requirements

Note: For patients who have had a whole blood transfusion, wait 10 days post transfusion to draw for genetic testing. No wait time is necessary for blood or saliva collection if the patient received leuko-reduced red cells or plasma.

 

Specimen: Whole blood, cord blood

Container(s): Lavender/EDTA, Yellow/ACD A or B

Preferred Vol: 3 mL

Minimum Vol: 1 mL

 

Note: Heparin samples (Green tops) are unacceptable.

 

Specimen: Extracted DNA from EDTA blood

Minimum: 10µg

Note: Isolation of nucleic acids for clinical testing must be performed in a CLIA-certified
laboratory or a laboratory meeting equivalent requirements as determined by the CAP
and/or the CMS. DNA concentration minimum 50 µg/mL; 260/280 ratio 1.70-2.00.

  

Specimen: Cultured cells

Acceptable:  Fibroblasts

Container(s): T-25 flasks

Preferred Vol: 2 flasks

 

Specimen: Saliva collected using Oragene Dx OGD-575/675 collection kit.

Container: Oragene Dx OGD-575/675 collection kit

IMPORTANT NOTE: Manufacturer instructions must be followed. The Oragene Dx OGD575/675 kit is not for children under 6 months. Contact Lab Client Services for more information or to obtain a kit 206-987-2617, labclientservices@seattlechildrens.org

Processing Instructions

Reject due to: Heparin

Spin: No

Aliquot: No

Temp: Refrigerate

Storage location: Molecular Genetics box in CPA refrigerator #2

 

Off-site collection: Refrigerate blood samples until ready to ship.  Transport all sample types at room temperature via overnight shipping.

Stability

Specimen Type Temperature Time
Cultured cells Room temp 3 days
Whole blood, extracted DNA Room temp 3-5 days
Whole blood, extracted DNA Refrigerated 7 days
Extracted DNA Frozen ok
Saliva, ORAgene Dx OGD-575/675 Room Temp 2 weeks

 

Note: Whole blood samples > 7days may be submitted to be assessed by our lab for acceptability for testing.

Availability

STAT Performed TAT
Contact lab Monday - Friday 2-3 weeks

 

Performing Laboratory

Seattle Children's Laboratory

Department

Department:  Molecular Genetics Laboratory

Phone: 206-987-3872

 

Lab Client Services: 206-987-2617

 

Lab Genetic Counselor: LabGC@seattlechildrens.org

CPT Codes

POLG full gene seq 81406
POLG targeted variant analysis 81403

 

Methodology

Method:

Full gene seq: bi-directional sequencing of all exons and exon-intron boundaries

Targeted variant sequencing: bi-directional sequencing of targeted variant(s)

 

Limitations: Mutations in the promoter region, large deletions, large duplications, or rare recombinant mutations may not be detected by this method.

Reference Range

Interpretive report will be provided

Requisition

Molecular Genetics

Special Instructions

Links to: POLG-Related Disorders GeneReview

Clinical Utility

DNA polymerase gamma is the only DNA polymerase found in the mitochondria and is responsible for mtDNA replication and repair. Mutations in the gene encoding polymerase gamma, POLG, cause mtDNA depletion or multiple mtDNA deletions resulting in a highly heterogeneous group of mitochondrial diseases. POLG mutations may account for up to 25% of all adult onset mitochondrial disease. POLG mutations have been described in Progressive External Ophthalmoplegia both autosomal dominant and recessive forms, parkinsonism and premature menopause, adult onset cerebellar ataxia, Sensory Ataxia Neuropathy with Opthalmoparesis (SANDO), Alpers Syndrome (childhood onset progressive spastic quadriparesis, progressive cerebral degeneration and liver failure) and other childhood or adulthood onset ataxia syndromes with and without seizures.