Spinocerebellar Ataxia Panel

General Information

Lab Name

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:

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

References

Schöls L, et al. Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol 1997, 42:924-32. 9403486
Goldfarb LG, et al. Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1. Ann Neurol 1996, 39:500-6. 8619528
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
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
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
Dürr A, et al. Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. Ann Neurol 1996, 39:490-9. 8619527
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
Stevanin G, et al. Clinical and molecular features of spinocerebellar ataxia type 6. Neurology 1997, 49:1243-6. 9371901
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
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
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

Code	Name
SCA1A1	ATXN1 (SCA1), allele 1
SCA1A2	ATXN1 (SCA1), allele 2
SCA2A1	ATXN2 (SCA2), allele 1
SCA2A2	ATXN2 (SCA2), allele 2
SCA3A1	ATXN3 (SCA3), allele 1
SCA3A2	ATXN3 (SCA3), allele 2
SCA6A1	CACNA1A (SCA6), allele 1
SCA6A2	CACNA1A (SCA6), allele 2
SCA7A1	ATXN7 (SCA7), allele 1
SCA7A2	ATXN7 (SCA7), allele 2
SCAITP	SCA Interpretation
SCACOM	SCA Comment
SCAPDI	SCA Panel Director

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

No mutation detected.

References

Schöls L, et al. Autosomal dominant cerebellar ataxia: phenotypic differences in genetically defined subtypes? Ann Neurol 1997, 42:924-32. 9403486
Goldfarb LG, et al. Unstable triplet repeat and phenotypic variability of spinocerebellar ataxia type 1. Ann Neurol 1996, 39:500-6. 8619528
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
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
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
Dürr A, et al. Spinocerebellar ataxia 3 and Machado-Joseph disease: clinical, molecular, and neuropathological features. Ann Neurol 1996, 39:490-9. 8619527
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
Stevanin G, et al. Clinical and molecular features of spinocerebellar ataxia type 6. Neurology 1997, 49:1243-6. 9371901
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
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
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

Collection

BLOOD:

Adult: 5 mL LAVENDER TOP tube
Child: 2 mL LAVENDER TOP tube
Also acceptable: YELLOW TOP (ACD) tube
Unacceptable: Heparin green top tubes

Forms & Requisitions

Genetics Requisition

Handling Instructions

Blood: Refrigerate whole blood up to 1 week.

Outside Laboratories: Ship whole blood at ambient temperature to arrive within 1 week of specimen collection.

Quantity

requested: Entire specimen
minimum: 1 mL whole blood

Processing

Processing: Blood: Refrigerate whole blood up to 1 week.
Transport Temperature

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: 206-598–0304 Lab email: genelab@uw.edu Tel (EXOME only): 206-543-0459	Manager Joe Bernal, jbernal@uw.edu Genetic Counselors Angela Jacobson, MS, LGC agibson@uw.edu Sandra Coe, MS,LGC, scoe20@uw.edu Dru Leistritz, MS, LGC, dru2@uw.edu (EXOME testing only) Daniel W. Serber, PhD, MS, LCGC, dwserber@uw.edu Variant Review Scientist Ankita Jhuraney, PhD Sarah Paolucci, MA, MS, LGC, spaolucc@uw.edu Catherine A. Darcey, MSc Faculty Colin C. Pritchard, MD, PhD Brian H. Shirts, MD, PhD Christina Lockwood, PhD, DABCC Stephen Salipante, MD, PhD Eric Konnick, MD, MS Niklas Krumm, MD,PhD Vera Paulson, MD, PhD Jillian Buchan, PhD, FACMG

Frequency

Performed weekly. Results within 2-3 weeks.

Available STAT?

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