Spinocerebellar Ataxia Panel

The dominant cerebellar ataxias are a clinically and genetically heterogeneous group of disorders that cannot be differentiated reliably from each other on a clinical basis. DNA testing is highly sensitive and specific and provides a definitive diagnosis for an estimated 50-60% of Caucasian patients with findings of dominant cerebellar ataxia. Patient DNA is analyzed to determine the number of CAG trinucleotide repeats located within each allele of the five causative genes; an abnormally large number of CAG repeats is diagnostic for the disease.

Two categories of tests are available:

• Spinocerebellar Ataxia Panel includes testing for all five types of SCA.
• Spinocerebellar Ataxia single test is offered to test for a single specific type: Spinocerebellar Ataxia 1 [SCA1T], Spinocerebellar Ataxia 2 [SCA2T], Spinocerebellar Ataxia 3 [SCA3T], Spinocerebellar Ataxia 6 [SCA6T], and Spinocerebellar Ataxia 7 [SCA7T].

Estimated Percent of Dominant Cerebellar Ataxias:

• Spinocerebellar Ataxia 1 (ATXN1) = 5-15%
• Spinocerebellar Ataxia 2 (ATXN2) = 10-15%
• Spinocerebellar Ataxia 3 (ATXN3) = 20-30%
• Spinocerebellar Ataxia 6 (CACNA1A) = 1-15%
• Spinocerebellar Ataxia 7 (ATXN7) = 1-5%

Notes:

• Frequencies of SCAs vary significantly in the Japanese and perhaps in other populations.
• Abnormal-sized ATXN7 alleles have been detected in ataxia patients without retinal degeneration.
• A DNA test for Friedreich ataxia, an autosomal recessive disorder, can be ordered separately (Online Test Guide Lab Mnemonic Friedreich's Ataxia DNA [FRDAX].

Indications for testing include:

• Symptomatic testing for patients with ataxia and a family history of ataxia
• Differential diagnosis for isolated cases of unexplained progressive ataxia (expect a relatively low positive rate)
• Presymptomatic testing for at-risk family members with appropriate genetic counseling

Polymerase Chain Reaction (PCR)/Capillary Electrophoresis.

The region containing the CAG repeat of the indicated gene for a specific type of spinocerebellar atxia (ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7) was amplified and fragment lengths determined by comparison to molecular weight standards after capillary electrophoresis. This test was developed and its performance characteristics determined by the Department of Laboratory Medicine at the University of Washington.

Acceptable:

1. Whole blood:5 mL lavender top (EDTA) tube or yellow (ACD) top tube or 2 mL microtainer lavender top tube
   
   
2. Extracted DNA from blood, chorionic villi, and amniocytes: 500 ng (concentration >10 ng/uL)
   
   
3. Cultured amniocytes/chorionic villi: MCC is required for testing fetal samples. See MCC OLTG.
   
   
4. Also acceptable, but requires the Genetics Director's approval and a backup culture. Direct chorionic villi and/or TISSUE: Send 20mg of tissue in a sterile tube or RPMI culture media
   
   *NOTE: If a fetal sample (cultured amniocytes or chorionic villi) was received, add MCC to the order. Prenatal testing requires concomitant testing for maternal cell contamination (see Online Test Guide, MCC for ordering and specimen requirements). See Special Instructions.

Unacceptable: Heparin green top tubes, buccal swab

SPS specimen handling:

1. Whole blood sample: store in the refrigerator
   
   
2. Cultured amniocytes/chorionic villi: store at room temperature. Call the Genetics lab upon receipt (206)598-7021.
   
   
3. Extracted DNA: store in the refrigerator

For clients outside of UW, please include any relevant clinical history.

If fetal tissue (cultured amniocytes or chorionic villi) was received for prenatal testing, consultation with the laboratory is required. Please notify the Genetics lab about prenatal studies via email at geneticshelp@uw.edu or call 206-598-7021.