Spinocerebellar Ataxia Panel

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General Information

Lab Name
Spinocerebellar Ataxia Panel
Lab Code
SCAPN
Epic Ordering
Spinocerebellar Ataxia Panel
Description

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:

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
References
  1. Schöls L, et al. Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol 1997, 42:924-32. 9403486
  2. Goldfarb LG, et al. Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1. Ann Neurol 1996, 39:500-6. 8619528
  3. Brandt V, Zoghbi HY. Spinocerebellar Ataxia Type 1. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997- . 1998 Oct 1 [updated 2017 Jun 22]. 20301363
  4. Geschwind DH, Perlman S, Figueroa CP, Treiman LJ, and Pulst SM. The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia. Am J Hum Genet 1997, 60:842-50. 9106530
  5. Pulst S-M. Spinocerebellar Ataxia Type 2. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997- . 1998 Oct 23 [updated 2019 Feb 14]. 20301452
  6. Dürr A, et al. Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. Ann Neurol 1996, 39:490-9. 8619527
  7. Paulson H. Spinocerebellar Ataxia Type 3. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997- . 1998 Oct 10 [updated 2015 Sep 24]. 20301375
  8. Stevanin G, et al. Clinical and molecular features of spinocerebellar ataxia type 6. Neurology 1997, 49:1243-6. 9371901
  9. Gomez CM. Spinocerebellar Ataxia Type 6. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-. 1998 Oct 23 [updated 2013 Jul 18]. 20301319
  10. Giunti P, et al. Molecular and clinical study of 18 families with ADCA type II: evidence for genetic heterogeneity and de novo mutation. Am J Hum Genet 1999, 64:1594-603. 10330346
  11. Garden G. Spinocerebellar Ataxia Type 7. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-. 1998 Aug 27 [updated 2012 Dec 20]. 20301433
Forms & Requisitions

Genetics Requisition

Synonyms
Ataxia Panel, MJD, SCA1, SCA2, SCA3, SCA6, SCA7
Components

Interpretation

Method

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.

Reference Range
See individual components
Ref. Range Notes
Normal Mutable Normal Intermediate Penetrance Full Penetrance
SCA1 Less than or equal to 44 repeats depending on the reflex testing 36-38 repeats 39-44 repeats, reflex testing required Greater than or equal to 44 repeats, depending on the reflex testing
SCA 2 <32 repeats 32 repeats >32 repeats
SCA 3 <45 repeats >44 repeats
SCA 6 <19 repeats 19 repeats 19 repeats >19 repeats
SCA 7 <19 repeats 28-33 repeats 34-36 repeats >36 repeats
References
  1. Schöls L, et al. Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol 1997, 42:924-32. 9403486
  2. Goldfarb LG, et al. Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1. Ann Neurol 1996, 39:500-6. 8619528
  3. Brandt V, Zoghbi HY. Spinocerebellar Ataxia Type 1. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997- . 1998 Oct 1 [updated 2017 Jun 22]. 20301363
  4. Geschwind DH, Perlman S, Figueroa CP, Treiman LJ, and Pulst SM. The prevalence and wide clinical spectrum of the spinocerebellar ataxia type 2 trinucleotide repeat in patients with autosomal dominant cerebellar ataxia. Am J Hum Genet 1997, 60:842-50. 9106530
  5. Pulst S-M. Spinocerebellar Ataxia Type 2. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997- . 1998 Oct 23 [updated 2019 Feb 14]. 20301452
  6. Dürr A, et al. Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. Ann Neurol 1996, 39:490-9. 8619527
  7. Paulson H. Spinocerebellar Ataxia Type 3. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997- . 1998 Oct 10 [updated 2015 Sep 24]. 20301375
  8. Stevanin G, et al. Clinical and molecular features of spinocerebellar ataxia type 6. Neurology 1997, 49:1243-6. 9371901
  9. Gomez CM. Spinocerebellar Ataxia Type 6. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-. 1998 Oct 23 [updated 2013 Jul 18]. 20301319
  10. Giunti P, et al. Molecular and clinical study of 18 families with ADCA type II: evidence for genetic heterogeneity and de novo mutation. Am J Hum Genet 1999, 64:1594-603. 10330346
  11. Garden G. Spinocerebellar Ataxia Type 7. In: GeneReviews at GeneTests: Medical Genetics Information Resource (database online). Copyright, University of Washington, Seattle. 1997-. 1998 Aug 27 [updated 2012 Dec 20]. 20301433
Guidelines

Ordering & Collection

Specimen Type
Blood/Cultured amniocytes or chorionic villus cells/Extracted DNA from blood, chorionic villi, and amniocyte. Direct chorionic villi, amniocyte, or amniotic fluid testing require Genetics Director approval. Please call the lab at 206-598-7021
Collection

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

Forms & Requisitions

Genetics Requisition

Handling Instructions

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
Quantity
requested: Entire specimen
minimum: Blood: 1 mL. If volume is less than 1mL, do not cancel. Send to Genetics lab. Confluent cultured cells: One (1) T25 flask. Extracted DNA: 250 ng

Processing

Processing

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.

Performance

LIS Dept Code
Genetics (GEN)
Performing Location(s)
UW-MT Genetics

Attention: Genetics Lab
Clinical lab, Room NW220
University of Washington Medical Center
1959 NE Pacific Street
Seattle, WA 98195

Tel: 206-598–6429 M–F (7:30 AM–4:00 PM)
Fax: 206-616-4584
Lab email: cgateam@uw.edu

Tel (EXOME only): 206-543-0459

Faculty
Jillian Buchan, PhD, FACMG
Runjun Kumar, MD, PhD
Regina Kwon, MD, MPH
Christina Lockwood, PhD, DABCC, DABMGG
Brian Shirts, MD, PhD
Abbye McEwen, MD, PhD
Colin Pritchard, MD, PhD
Vera Paulson, MD, PhD
Eric Konnick, MD, MS
He Fang, PhD
Frequency
Performed weekly. Results within 2-3 weeks.
Available STAT?
No

Billing & Coding

CPT codes
81178, 81179, 81180, 81181, 81184
Billing Comments

For pricing information, contact Client Support Services 206-520-4600 or 800-713-5198.

LOINC
26435-8
Interfaced Order Code
UOW587