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Test Code CSTB CSTB Gene, Repeat Expansion Analysis, Varies


Ordering Guidance


This test only detects dodecamer repeat expansions. If testing for both dodecamer repeat expansions and other CSTB variants is requested, order a custom gene panel for the CSTB gene. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, Varies.



Shipping Instructions


 



Specimen Required


Patient Preparation: A previous hematopoietic stem cell transplant from an allogenic donor will interfere with testing. For information about testing patients who have received a hematopoietic stem cell transplant, call 800-533-1710.

 

Submit only 1 of the following specimens:

 

Specimen Type: Whole blood

Container/Tube:

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

Acceptable: Green top (sodium heparin)

Specimen Volume: 3 mL

Collection Instructions:

1. Invert several times to mix blood.

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

3. Whole blood collected postnatal from an umbilical cord is also acceptable. See Additional Information.

Specimen Stability Information: Ambient 4 days (preferred)/Refrigerated 4 days/Frozen 4 days

Additional Information:

1. Specimens are preferred to be received within 4 days of collection. Extraction will be attempted for specimens received after 4 days, and DNA yield will be evaluated to determine if testing may proceed.

2. To ensure minimum volume and concentration of DNA are met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.

3. For postnatal umbilical cord whole blood specimens, maternal cell contamination studies are recommended to ensure test results reflect that of the patient tested.  A maternal blood specimen is required to complete maternal cell contamination studies. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on both the cord blood and maternal blood specimens under separate order numbers.

 

Specimen Type: Extracted DNA

Container/Tube:

Preferred: Screw Cap Micro Tube, 2 mL with skirted conical base

Acceptable: Matrix tube, 1 mL

Collection Instructions:

1. The preferred volume is at least 100 mcL at a concentration of 75 ng/mcL.

2. Include concentration and volume on tube.

Specimen Stability Information: Frozen (preferred) 1 year/Ambient/Refrigerated

Additional Information: DNA must be extracted in a CLIA-certified laboratory or equivalent and must be extracted from a specimen type listed as acceptable for this test (including applicable anticoagulants). Our laboratory has experience with Chemagic, Puregene, Autopure, MagnaPure, and EZ1 extraction platforms and cannot guarantee that all extraction methods are compatible with this test. If testing fails, one repeat will be attempted, and if unsuccessful, the test will be reported as failed and a charge will be applied. If applicable, specific gene regions that were unable to be interrogated due to DNA quality will be noted in the report.


Forms

1. New York Clients-Informed consent is required. Please 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 CSTB-related progressive myoclonic epilepsy

 

Identifying full penetrance dodecamer repeat expansions within CSTB known to cause CSTB-related progressive myoclonic epilepsy, allowing for predictive testing of at-risk family members

 

Impacting patient treatment and management through the identification of a specific underlying etiology for epilepsy (eg, directing appropriate use of anti-epileptic drugs and other treatment modalities)

Genetics Test Information

This test assesses for CCC-CGC-CCC-GCG dodecamer repeat expansions in the promoter region of CSTB to confirm a molecular diagnosis of CSTB-related progressive myoclonic epilepsy, also known as progressive myoclonic epilepsy type 1 (EPM1).

Method Name

Polymerase Chain Reaction (PCR)

Reporting Name

CSTB, Repeat Expansion Analysis

Specimen Type

Varies

Specimen Stability Information

Specimen Type Temperature Time
Varies Varies

Reject Due To

All specimens will be evaluated by Mayo Clinic Laboratories for test suitability.

Clinical Information

CSTB-related progressive myoclonus epilepsy (PME), also known as progressive myoclonus epilepsy type 1 (EPM1) or Unverricht-Lundborg disease, is the most common and least severe of the collective progressive myoclonus epilepsies. CSTB-related PME is inherited in an autosomal recessive pattern and is associated with inter- and intrafamilial variability.(1) Individuals with CSTB-related PME have normal early development with onset of symptoms typically in the first or second decade of life. CSTB-related PME is characterized by involuntary myoclonus that is action- or stimulus-precipitated. Individuals with the condition are at increased risk for seizures, including tonic-clonic, absence, psychomotor and focal motor. The condition is progressive, leading to wheelchair dependence in some individuals. Later symptoms may also include ataxia, incoordination, intention tremor, dysarthria, mood disorders, and mild cognitive decline.(1-4)

 

CSTB-related PME is caused by disease-causing variants in the CSTB gene. An expansion of a dodecamer repeat sequence in the promoter region of the CSTB gene accounts for approximately 90% of disease-causing variants (99% in Finnish individuals). Full penetrance CSTB expansions are greater than or equal to 30 repeats, while normal alleles are typically 2 or 3 repeats. Allele sizes between 5 and 29 repeats are of unclear significance. The remainder of disease-causing variants are sequence variants including missense, nonsense, splice site variants, and small deletions and duplications.(1)

 

Genotype/phenotype correlation suggests that individuals who are homozygous for nonexpansion variants or compound heterozygous for one expansion allele and one nonexpansion allele have earlier onset and more severe symptoms than those individuals with biallelic expansion alleles.(4) Instability of the repeat expansion has been reported with vertical transmission, including both minimal expansion and contraction of repeat sizes.(2) Alleles in the uncertain range are not associated with symptoms of CSTB-related PME but may demonstrate instability with transmission.(1) Since repeat alleles in this size range have rarely been reported, the risk of repeat expansion into the full penetrance allele range (>29 repeats) is not fully understood. Additionally, correlation of repeat size with onset of symptoms is unclear.

Reference Values

Normal: <5 dodecamer repeats

Repeat Size of Uncertain Significance: 5-29 dodecamer repeats

Full Penetrance Expansion: >29 dodecamer repeats

An interpretive report will be provided.

Interpretation

The interpretive report includes an overview of the findings as well as the associated clinical significance.

Cautions

For predictive testing, it is important to first document the molecular etiology of disease in an affected family member to confirm that a CSTB repeat expansion is the underlying mechanism of disease in the family. Specifically, this assay will not detect nonrepeat expansion variants and progressive myoclonic epilepsy may be caused by variants in other genes.

 

It is recommended that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.

 

Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in test interpretation may occur if the provided information is inaccurate or incomplete.

 

Rare variants (ie, polymorphisms) exist which could lead to false-negative results.

 

Bone marrow transplants from allogenic donors will interfere with testing. Call Mayo Clinic Laboratories for instructions for testing patients who have received a bone marrow transplant.

Method Description

A combined amplicon-length and repeat-primed polymerase chain reaction-based assay is utilized to detect expansions of a dodecamer repeat region in the CSTB gene.(Unpublished Mayo method)

Day(s) Performed

Varies

Report Available

14 to 28 days

Specimen Retention Time

Whole blood: 28 days (if available); Extracted DNA: 3 months

Performing Laboratory

Mayo Clinic Laboratories in Rochester

Test Classification

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

CPT Code Information

81188

LOINC Code Information

Test ID Test Order Name Order LOINC Value
CSTB CSTB, Repeat Expansion Analysis 41110-8

 

Result ID Test Result Name Result LOINC Value
616516 Result Summary 50397-9
616517 Result 82939-0
616518 Interpretation 69047-9
616519 Reason for Referral 42349-1
616520 Specimen 31208-2
616521 Method 85069-3
616522 Source 31208-2
616523 Released By 18771-6

Testing Algorithm

For cord blood specimens that have an accompanying maternal blood specimen, maternal cell contamination studies will be performed at an additional charge.

 

For more information see Epilepsy: Unexplained Refractory and/or Familial Testing Algorithm

Reflex Tests

Test ID Reporting Name Available Separately Always Performed
MATCC Maternal Cell Contamination, B Yes No