Spinocerebellar Ataxia Type 3 Expansion Analysis

Clinical Information

Spinocerebellar ataxia type 3, also known as Machado-Joseph disease, is the most common form of hereditary spinocerebellar ataxia . Features include lack of coordination and balance, gait abnormalities, vision problems such as nystagmus and ophthalmoplegia, dysphagia, and dysarthria. Parkinsonism develops over time including spasticity, rigidity, dystonia, and tremor. Peripheral neuropathy, muscle weakness, and fasciculations may occur. Average age of onset ranges form the teens to the 40s, and lifespan is typically reduced.

SCA3 is inherited in an autosomal dominant pattern, and it is caused by a CAG trinucleotide repeat expansion in the ATXN3 gene. Repeat ranges are as follows: Normal (≤ 44), Intermediate (45-59), Pathogenic (≥ 60). Intermediate alleles may have incomplete penetrance, and the age of onset and rate of progression correlate with the size of the expansion.

Technical Information

• This test is performed using triplet repeat-primed PCR.
• Genomic DNA is analyzed for trinucleotide (CAG) repeat expansion in the ATXN3 gene. The triplet repeat-primed polymerase chain reaction (TP-PCR) assay used for analysis is based on a method described by Cagnoli et al. (J Mol Diagn. 2018 May;20(3):289-297).
• The number of trinucleotide repeats in the ATXN3 gene is briefly analyzed using TP-PCR and capillary electrophoresis followed by data analysis using GeneMarker software.

Specimen Requirements

• The preferred sample type is 3-4 ml of peripheral blood collected in an EDTA (purple top) tube. Extracted DNA and saliva are also accepted for this test. Blood and saliva kits are available by request.
• Send approximately 5µg of extracted DNA at a requested concentration of 90-130 ng/µl.
• Saliva samples must be submitted in an approved saliva kit, and sample kits are available upon provider request.

Transport Instructions

• The blood 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.
• Extracted DNA should be sent at room temperature via overnight delivery.
• Saliva is stable at room temperature and can be delivered via overnight or ground shipping.