POLG1-related disorders : POLG1 Sequencing

Test Information

POLG1 sequencing is a molecular test used to identify variants in the gene associated with POLG1-related disorders including Progressive External Ophthalmoplegia.

Turnaround Time

3 weeks

CPT Code(s)

81406

Cost

$1,500

Genes

Clinical Information

POLG1 mutations are responsible for multiple clinical diagnoses with overlapping phenotypes. Aside from Autosomal Dominant Progressive External Ophthalmoplegia, all of the other conditions are inherited in an autosomal recessive manner.
Alpers-Huttenlocher syndrome (AHS) includes a progressive and severe encephalopathy with epilepsy, neuropathy and liver failure.
Childhood Myocerebrohepatopathy Spectrum (MCHS) presents before age three with developmental delay, lactic acidosis, failure to thrive and myopathy. Hearing loss, cyclic vomiting, renal and hepatic problems are also often present.
Myoclonic Epilepsy Myopathy Sensory Ataxia (MEMSA) includes myopathy, epilepsy and ataxia without ophthalmoplegia and generally presents in young adulthood.
Ataxia Neuropathy Spectrum (ANS) includes mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). Features include ataxia, neuropathy and often encephalopathy with seizures.
Autosomal Recessive Progressive External Ophthalmoplegia (arPEO) involves progressive PEO without systemic involvement.
Autosomal Dominant Progressive External Ophthalmoplegia (adPEO) involves progressive weakness of the extraocular eye muscles which causes strabismus and ptosis.

Indications

Molecular testing is useful to confirm the diagnosis and to identify the disease causing mutations within a family to allow for carrier testing and prenatal diagnosis.

Methodology

Sanger Sequencing

Detection

Sequencing of the gene will detect mutations approximately 95% of individuals with a POLG1-related disorder.

Specimen Requirements

5 to 7 ml of peripheral blood collected in an EDTA (lavender top) tube is the preferred specimen type. The minimal blood needed for reliable DNA isolation is 3 ml. Extracted DNA, dried blood spots, and saliva are also accepted for this test.

Transport Instructions

The specimen should be kept at room temperature and delivered via overnight shipping. If shipment is delayed by one or two days, the specimen should be refrigerated and shipped at room temperature. Do not freeze the specimen. Samples collected on Friday can be safely designated for Monday delivery.

Prenatal Testing Information

Prenatal diagnosis is available if the familial mutations are known. Additional fees for cell culture and maternal cell contamination may apply. Maternal cell contamination studies are required for all prenatal molecular tests. Contact the laboratory prior to sending a prenatal specimen.

Have Questions Need Support?

Call our laboratory at 1-800-473-9411 or contact one of our Laboratory Genetic Counselors for assistance.
Robin Fletcher, MS, CGC
Kellie Walden, MS, CGC

Molecular Testing, Sanger Sequencing
Lucy's Story

Lucy's Story

When our daughter Lucy had a metabolic crisis at 7 days old, we were shocked and devastated to find out that she was born with a rare genetic disorder (MSUD). Her newborn screening results did not make it back in time to prevent the crisis, and no one at our local hospital was familiar with the disease. They did not know how to treat her. Calls were made to Greenwood Genetic Center to confirm her diagnosis...

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