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Test ID: SCARA Spinocerebellar Ataxia Type 1, 2, 3, 6, or 7, Repeat Expansion Analysis, Varies


Ordering Guidance


This test is not a gene panel for all types of spinocerebellar ataxia (SCA). If individual findings are not specific for one type of SCA, panel analysis is available and includes testing for SCA1, 2, 3, 6, and 7; order SCAP / Spinocerebellar Ataxia Repeat Expansion Panel, Varies.



Shipping Instructions


Specimen preferred to arrive within 96 hours of collection.



Necessary Information


The type of spinocerebellar ataxia (SCA) to be assessed (SCA1, 2, 3, 6, or 7) is required. This information must be provided for testing to be performed.



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.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

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 whole blood specimen in original tube. Do not aliquot.

Specimen Stability Information: Ambient (preferred) 96 hours/Refrigerated

 

Due to the complexity of prenatal testing, consultation with the laboratory is required for all prenatal testing. Prenatal specimens can be sent Monday through Thursday and must be received by 5 p.m. Central time on Friday in order to be processed appropriately. All prenatal specimens must be accompanied by a maternal blood specimen. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.

 

Specimen Type: Amniotic fluid

Container/Tube: Amniotic fluid container

Specimen Volume: 20 mL

Specimen Stability Information: Refrigerated (preferred)/Ambient

Additional information: A separate culture charge will be assessed under CULAF / Culture for Genetic Testing, Amniotic Fluid. An additional 2 to 3 weeks is required to culture amniotic fluid before genetic testing can occur.

 

Specimen Type: Chorionic villi

Container/Tube: 15-mL tube containing 15 mL of transport media

Specimen Volume: 20 mg

Specimen Stability Information: Refrigerated

Additional Information: A separate culture charge will be assessed under CULFB / Fibroblast Culture for Molecular Testing, Chorionic Villi/Products of Conception.

 

Acceptable:

Specimen Type: Confluent cultured cells

Container/Tube: T-25 flask

Specimen Volume: 2 Flasks

Collection Instructions: Submit confluent cultured cells from another laboratory.

Specimen Stability Information: Ambient (preferred)/Refrigerated


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 type 1, 2, 3, 6, or 7

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
CULFB Fibroblast Culture for Genetic Test Yes No
CULAF Amniotic Fluid Culture/Genetic Test Yes No
MATCC Maternal Cell Contamination, B Yes No

Testing Algorithm

For prenatal specimens only: If amniotic fluid (nonconfluent cultured cells) is received, amniotic fluid culture will be added and charged separately. If chorionic villus specimen (nonconfluent cultured cells) is received, fibroblast culture for genetic test will be added and charged separately. For any prenatal specimen that is received, maternal cell contamination studies will be added.

Method Name

Polymerase Chain Reaction (PCR)

Reporting Name

SCA 1,2,3,6, or 7 Repeat Analysis

Specimen Type

Varies

Specimen Minimum Volume

Amniotic fluid: 10 mL
Blood: 0.5 mL
Chorionic villi: 5 mg

Specimen Stability Information

Specimen Type Temperature Time Special Container
Varies Varies

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

88233-Fibroblast Culture (if appropriate)

88235-Amniotic Fluid Culture (if appropriate)

88240-Cryopreservation (if appropriate)

81265-Maternal Cell Contamination (if appropriate)

81178 (if appropriate)

81179 (if appropriate)

81180 (if appropriate)

81181 (if appropriate)

81184 (if appropriate)

LOINC Code Information

Test ID Test Order Name Order LOINC Value
SCARA SCA 1,2,3,6, or 7 Repeat Analysis In Process

 

Result ID Test Result Name Result LOINC Value
609700 Result Summary 21769-5
MG323 Test Code 21768-7
609701 Result 36911-6
609702 Interpretation 69047-9
609703 Reason for Referral 42349-1
609704 Specimen 31208-2
609705 Source 31208-2
609706 Method 85069-3
609707 Disclaimer 62364-5
609708 Released By 18771-6
Mayo Clinic Laboratories | Neurology Catalog Additional Information:

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