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Test ID: SCAP Spinocerebellar Ataxia Repeat Expansion Panel, Varies


Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Specimen Required


Patient Preparation: A previous bone marrow transplant from an allogenic donor will interfere with testing. Call 800-533-1710 for instructions for testing patients who have received a bone marrow transplant.

 

Container/Tube:

Preferred: Lavender top (EDTA) or yellow top (ACD)

Acceptable: Any anticoagulant

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

2. Send specimen in original tube. Do not aliquot.


Forms

1. New York Clients-Informed consent is required. Document on the request form or electronic order that a copy is on file. The following documents are available:

-Informed Consent for Genetic Testing (T576)

-Informed Consent for Genetic Testing-Spanish (T826).

2. Molecular Genetics: Neurology Patient Information

3. If not ordering electronically, complete, print, and send a Neurology Specialty Testing Client Test Request (T732) with the specimen.

Useful For

Molecular confirmation of clinically suspected spinocerebellar ataxia

Method Name

Polymerase Chain Reaction (PCR)

Reporting Name

Spinocerebellar Ataxia Panel

Specimen Type

Varies

Specimen Minimum Volume

0.5 mL

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Ambient (preferred)
  Frozen 
  Refrigerated 

Clinical Information

Spinocerebellar Ataxia Type 1:

Spinocerebellar ataxia type 1 (SCA1) is characterized by progressive ataxia, dysarthria, eventual deterioration of bulbar functions, and ophthalmoplegia. Onset typically occurs in the 3rd to 4th decade of life. Most individuals present with difficulties in gait or slurred speech. SCA1 is caused by an expansion of the cytosine-adenine-guanine (CAG) trinucleotide repeat in the ATXN1 gene. This trinucleotide repeat is polymorphic in the general population, with the number of benign repeats ranging from 6 to 37. The pathogenicity of the repeat is dependent on the presence or absence of cytosine-adenine-thymine (CAT) trinucleotide repeats that interrupt the CAG repeats. Therefore, individuals with 36 to 37 uninterrupted CAG repeats are predisposed to having a child with an expanded allele. In affected individuals, the CAG expansions are greater than 38 uninterrupted CAG repeats or greater than 44 repeats regardless of the presence or absence of CAT repeat interruptions. The presence of CAT repeats in an individual with 36 to 43 repeats is considered normal and not pathogenic. In contrast, 38 repeats without CAT repeats is of uncertain significance. There is a report of an individual with very last onset SCA1 with 38 repeats. Reduced penetrance has been associated with 44 repeats. As with other trinucleotide repeat disorders, large CAG expansions are associated with earlier onset and a more severe clinical course.

 

SCA2:

Spinocerebellar ataxia type 2 (SCA2) is characterized by slowly progressive ataxia and dysarthria, and slow saccadic eye movements. The mean age of onset is in the 4th decade, but symptoms may appear from childhood to later adulthood. SCA2 is caused by an expansion of the CAG trinucleotide repeat in the ATXN2 gene. This trinucleotide repeat is polymorphic in the general population, with the number of benign repeats less than 32. However, 29 to 31 heterozygous repeats have been associated with an increased exponential risk for amyotrophic lateral sclerosis (ALS). Additionally, there has been a report of an individual homozygous for 31 repeats with late onset cerebellar ataxia. In contrast, 27 repeats have been associated with a protective effect for ALS. In affected individuals the CAG expansion is greater than 34 repeats, with the most common disease-causing alleles have 37 to 39 repeats. Larger CAG expansions are associated with an earlier age of onset but repeat length cannot predict age of onset or disease severity. A CAG expansion of 32 repeats is of unclear clinical significance. Repeats in the 33 to 34 range are associated with reduced penetrance.

 

SCA3:

Spinocerebellar ataxia type 3 (SCA3), also known as Machado-Joseph disease, is characterized by progressive cerebellar ataxia and pyramidal signs. The age of onset is highly variable but most commonly occurs in the 2nd to 5th decade of life. Individuals may present with gait problems, speech difficulties, clumsiness, or visual blurring. SCA3 is caused by an expansion of the CAG trinucleotide repeat in the ATXN3 gene. This trinucleotide repeat is polymorphic in the general population, with the number of benign repeats ranging from 12 to 44. In affected individuals the CAG expansion ranges from 60 to 87 repeats. A loose correlation exists between repeat length and clinical phenotype. Individuals with 45 to 59 CAG repeats are predisposed to having a child with an expanded allele and may or may not have symptoms themselves. There have been reports of reduced penetrant and nonpenetrant alleles with repeats in this range.

 

SCA6:

Spinocerebellar ataxia type 6 (SCA6) is characterized by adult-onset, slowly progressive cerebellar ataxia, dysarthria, and nystagmus. The mean age of onset is 43 to 52 years. Initial symptoms include unsteadiness, stumbling, and imbalance. SCA6 is caused by an expansion of the CAG trinucleotide repeat in the CACNA1A gene. This trinucleotide repeat is polymorphic in the general population, with the number of benign repeats less than 19. In affected individuals the CAG expansion ranges from 20 to 33 repeats. Larger CAG expansions are associated with an earlier age of onset. A CAG expansion of 19 repeats is of unclear clinical significance. Individuals with 19 CAG repeats are predisposed to having a child with an expanded allele. Additionally, homozygous abnormal expansions have been reported in individuals with younger age of onset and a more severe phenotype.

 

SCA7:

Spinocerebellar ataxia type 7 (SCA7) is characterized by progressive cerebellar ataxia, including dysarthria and dysphagia, and con-rod and retinal dystrophy. Onset ranges from infancy to the 5th or 6th decade of life. SCA7 is caused by an expansion of the CAG trinucleotide repeat in the ATXN7 gene. This trinucleotide repeat is polymorphic in the general population, with the number of benign repeats less than 19. In affected individuals the CAG expansion is greater than 36 repeats. A CAG expansion of 19 to 27 repeats is of unclear clinical significance. Individuals with 28 to 33 repeats are predisposed to having a child with an expanded allele but are unlikely to have symptoms themselves. Thirty-four to 36 repeats is associated with reduced-penetrance, and when symptoms do occur, they are more likely to be associated with later onset and a milder phenotype.

Reference Values

SPINOCEREBELLAR ATAXIA TYPE 1

Normal alleles: <36 CAG repeats

Normal alleles with CAT interruptions: 36-43 repeats

Intermediate alleles without CAT interruptions: 36-37 repeats

Uncertain significance: 38 repeats

Expanded alleles without CAT interruptions: >38 CAG repeats

Expanded alleles with CAT interruptions: >43 CAG repeats

 

SPINOCEREBELLAR ATAXIA TYPE 2

Normal alleles: <32 repeats

Uncertain significance: 31 homozygous and 32 repeats

Reduced penetrance: 33-34 repeats

Expanded alleles: >34 repeats

 

SPINOCEREBELLAR ATAXIA TYPE 3

Normal alleles: <45 repeats

Intermediate alleles: 45-59 repeats

Expanded alleles: >59 repeats

 

SPINOCEREBELLAR ATAXIA TYPE 6

Normal alleles: <19 repeats

Intermediate alleles: 19 heterozygous repeats

Uncertain significance: 19 homozygous repeats

Expanded alleles: >19 repeats

 

SPINOCEREBELLAR ATAXIA TYPE 7

Normal alleles: <19 repeats

Uncertain significance: 19-27 repeats

Intermediate alleles: 28-33 repeats

Reduced penetrance: 34-36 repeats

Expanded alleles: >36 repeats

 

An interpretive report will be provided.

Interpretation

An interpretive report will be provided.

Clinical Reference

1. Soong BW, Morrison PJ: Spinocerebellar ataxias. Handb Clin Neurol. 2018;155:143-174. doi: 10.1016/B978-0-444-64189-2.00010-X

2. Buijsen RAM, Toonen LJA, Gardiner SL, et al: Genetics, mechanisms, and therapeutic progress in polyglutamine spinocerebellar ataxias. Neurotherapeutics. 2019 Apr;16(2):263-286. doi: 10.1007/s13311-018-00696-y

Day(s) Performed

Monday, Wednesday

Report Available

14 to 21 days

Test Classification

This test was developed, and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the US Food and Drug Administration.

CPT Code Information

81178

81179

81180

81181

81184

81479 (if appropriate for government payers)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SCAP Spinocerebellar Ataxia Panel In Process

 

Result ID Test Result Name Result LOINC Value
609506 Result Summary 21769-5
609507 Result 36911-6
609508 Interpretation 69047-9
609509 Additional Information 48767-8
609510 Specimen 31208-2
609511 Source 31208-2
609512 Method 85069-3
609513 Disclaimer 62364-5
609514 Released By 18771-6
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

mml-Movement-Disorders