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HelpTest Code C9ORF C9orf72 Hexanucleotide Repeat, Molecular Analysis, Varies
Useful For
Molecular confirmation of clinically suspected cases of c9FTD/ALS, frontotemporal dementia (FTD), or amyotrophic lateral sclerosis (ALS)
Presymptomatic testing for individuals with a family history of c9FTD/ALS and a documented expansion in the C9orf72 gene
Special Instructions
Method Name
Polymerase Chain Reaction (PCR)
Reporting Name
C9orf72, Molecular AnalysisSpecimen Type
VariesShipping Instructions
Specimen Required
Patient Preparation: A previous bone marrow transplant from an allogeneic donor will interfere with testing. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Submit only 1 of the following specimens:
Specimen Type: Whole blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD)
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) 4 days/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 is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
Specimen Type: Cord blood
Container/Tube: Lavender top (EDTA) or yellow top (ACD)
Specimen Volume: 3 mL
Collection Instructions:
1. Invert several times to mix blood.
2. Send cord blood specimen in original tube. Do not aliquot.
Specimen Stability Information: Ambient (preferred) 4 days/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 is met, the requested volume must be submitted. Testing may be canceled if DNA requirements are inadequate.
3. While a properly collected cord blood sample may not be at risk for maternal cell contamination, unanticipated complications may occur during collection. Therefore, maternal cell contamination studies are recommended to ensure the test results reflect that of the patient tested and are available at an additional charge. Order MATCC / Maternal Cell Contamination, Molecular Analysis, Varies on the maternal specimen.
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.
Specimen Minimum Volume
See Specimen Required
Specimen Stability Information
| Specimen Type | Temperature | Time |
|---|---|---|
| Varies | Varies | |
Reject Due To
All specimens will be evaluated at Mayo Clinic Laboratories for test suitability.Clinical Information
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease affecting the upper and lower motor neurons. The disease is characterized by progressive spasticity, muscle wasting and paralysis, typically leading to death from respiratory failure.
Frontotemporal dementia (FTD) is a dementia syndrome that predominantly involves the frontal and temporal lobes of the brain. Clinical presentation is variable and includes progressive changes in behavior and personality and language disturbances. Affected individuals may also exhibit extrapyramidal signs.
Amyotrophic lateral sclerosis and FTD are now thought to represent an overlapping spectrum of disease. Recent literature has found that approximately 40% of familial ALS, 25% of familial FTD, and 90% of familial ALS/FTD cases have a large hexanucleotide repeat (GGGGCC) expansion in a noncoding region of C9orf72. At lower frequency, C9orf72 hexanucleotide repeat expansions have also been observed in individuals with sporadic ALS, FTD, and ALS/FTD. The vast majority of individuals affected with a C9orf72-related disorder (c9ALS, c9FTD, or c9ALS/FTD) have hexanucleotide repeat expansions in the hundreds to thousands, while unaffected individuals have repeat sizes less than 20. The significance of repeat sizes between 20 and 100 repeats is currently unclear as both healthy controls and individuals with ALS or FTD phenotypes have been reported with repeat sizes in this range.
Reference Values
Normal alleles (reference):<20 GGGGCC repeats
Indeterminate alleles: 20-100 GGGGCC repeats
Pathogenic alleles: >100* GGGGCC repeats
*The exact cutoff for pathogenicity is currently undefined. Although additional studies are needed to confirm if 100 repeats is the cutoff for pathogenicity, most individuals affected with a C9orf72-related disorder have C9orf72 hexanucleotide repeat expansions with hundreds to thousands of 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 presence of the hexanucleotide repeat expansion in the C9orf72 gene in an affected family member to confirm that the repeat expansion is the underlying mechanism of disease in the family.
It is strongly recommended that patients undergoing predictive testing receive genetic counseling both prior to testing and after results are available.
Predictive testing of an asymptomatic child is not recommended.
Test results should be interpreted in the context of clinical findings, family history, and other laboratory data. Errors in the interpretation of results may occur if information given is inaccurate or incomplete.
Due to somatic mosaicism, repeat size identified in the peripheral blood specimen may not reflect the repeat size in untested tissues (eg, central nervous system). In addition, a negative result does not rule out the presence of a mutation in the mosaic state that may be present but below the limit of detection of this assay (approximately 5%).
Rare sequence variants immediately downstream of the C9orf72 repeat region may interfere with genotype results but are not expected to affect repeat-primed peaks.
Rare undocumented variants (ie, polymorphisms) in the polymerase chain reaction primer binding regions may lead to false-negative results.
This test does not assess the methylation status of the C9orf72 gene.
Method Description
A combined amplicon-length and repeat-primed polymerase chain reaction-based assay is utilized to size alleles up to approximately 145 repeats and detect expansions of GGGGCC hexanucleotide repeat region in the C9orf72 gene.(Ida CM, Lundquist PA, Bram E, et al. Evaluation of single-tube combined amplicon-length and repeat-primed long-read PCR assay for clinical detection and characterization of C9orf72 hexanucleotide repeat expansion. Abstract 731. 2017 ACMG Annual Clinical Genetics Meeting. Phoenix, AZ, March 23, 2017)
Day(s) Performed
Varies
Report Available
21 to 28 daysSpecimen Retention Time
Whole blood: 30 days (if available); Extracted DNA: 3 monthsPerforming 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
81479
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| C9ORF | C9orf72, Molecular Analysis | 81846-8 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 52852 | Result Summary | 50397-9 |
| 52853 | Result | 77635-1 |
| 52854 | Interpretation | 69047-9 |
| 52855 | Reason for Referral | 42349-1 |
| 52856 | Specimen | 31208-2 |
| 55158 | Method | 85069-3 |
| 52857 | Source | 31208-2 |
| 52858 | Released By | 18771-6 |
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.
Testing Algorithm
For more information see Inherited Motor Neuron Disease and Dementia Testing Algorithm