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HelpTest ID: AFTDP Inherited Frontotemporal Dementia and Amyotrophic Lateral Sclerosis Gene Panel, Varies
Ordering Guidance
First tier testing for a diagnosis of dementia or amyotrophic lateral sclerosis is C9ORF / C9orf72, Hexanucleotide Repeat, Molecular Analysis, Varies, which is included with this test but is also available separately.
Targeted testing for familial variants (also called site-specific or known mutations testing) is available for the genes on this panel. See FMTT / Familial Variant, Targeted Testing, Varies. To obtain more information about this testing option, call 800-533-1710.
Customization of this panel and single gene analysis for any gene present on this panel are available. For more information see CGPH / Custom Gene Panel, Hereditary, Next-Generation Sequencing, 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. For instructions for testing patients who have received a bone marrow transplant, call 800-533-1710.
Specimen Type: Whole blood
Container/Tube: 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.
Specimen Stability Information: Ambient (preferred)/Refrigerated
Additional Information: To ensure minimum volume and concentration of DNA is met, the preferred volume of blood must be submitted. Testing may be canceled if DNA requirements are inadequate.
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
Establishing a molecular diagnosis for patients with frontotemporal dementia (FTD) and/or amyotrophic lateral sclerosis (ALS)
Identifying variants within genes known to be associated with FTD and/or ALS, allowing for predictive testing of at-risk family members
Genetics Test Information
This test utilizes next-generation sequencing to detect single nucleotide and copy number variants in 51 genes associated with frontotemporal dementia and/or amyotrophic lateral sclerosis: ALS2, ANG, ANXA11, APP, ASAH1, CCNF, CHCHD10, CHMP2B, CSF1R, DCTN1, ERBB4, FIG4, FUS, GRN, HEXB, HNRNPA1, HNRNPA2B1, ITM2B, KIF5A, MAPT, MATR3, NEFH, NOTCH3, NPC1, NPC2, OPTN, PANK2, PFN1, PRNP, PSEN1, PSEN2, SETX, SIGMAR1, SNCA, SOD1, SPG11, SPTLC1, SQSTM1, TAF15, TARDBP, TBK1, TBP, TIA1, TIMM8A, TREM2, TUBA4A, TYROBP, UBQLN2, VAPB, VCP, and VRK1. A polymerase chain reaction-based assay is utilized to detect C9orf72 GGGGCC hexanucleotide repeat expansions. See Targeted Genes and Methodology Details for Inherited Frontotemporal Dementia and Amyotrophic Lateral Sclerosis Gene Panel and Method Description for additional details.
Identification of a disease-causing variant may assist with diagnosis, prognosis, clinical management, recurrence risk assessment, familial screening, and genetic counseling for frontotemporal dementia and/or amyotrophic lateral sclerosis.
Method Name
Sequence Capture and Targeted Next-Generation Sequencing followed by Polymerase Chain Reaction (PCR) and Sanger Sequencing
Reporting Name
FTD and ALS Gene PanelSpecimen Type
VariesSpecimen Minimum Volume
1 mL
Specimen Stability Information
| Specimen Type | Temperature | Time | Special Container |
|---|---|---|---|
| Varies | Varies | ||
Clinical Information
Frontotemporal dementia (FTD) is a progressive neurodegenerative syndrome that affects the frontal and temporal cerebral cortices. Clinical presentation is variable and includes changes in behavior, difficulties with language, rigidity, palsy, and saccadic (rapid) eye movement. Symptoms generally begin between 40 and 60 years of age, with a mean age of onset at approximately 45 years. They typically last between 5 and 10 years, progressing to severe dementia and mutism. The presentation of frontotemporal dementia may be confused with other dementias, including Alzheimer disease. It is important to distinguish between these different dementias because progression and patient management are different for the various dementias.
Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with progressive loss of upper and lower motor neurons. ALS typically presents with progressive muscle wasting, hyperreflexia, and spasticity. Death from respiratory failure usually occurs within 3 to 5 years of disease onset.
FTD and ALS are thought to represent a continuous disease spectrum. However, the molecular mechanism underlying the co-occurrence of FTD and ALS remains unclear. In some individuals ALS occurs first, while in others FTD precedes ALS by several years. Between 40% and 50% of individuals with ALS present with an FTD-associated clinical phenotype.
Given the clinical overlap of FTD and ALS, this multigene panel includes genes associated with FTD and ALS.
Reference Values
An interpretive report will be provided.
C9orf72 Repeats:
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 the cutoff for pathogenicity is 100 repeats, most individuals affected with a C9orf72-related disorder have C9orf72 hexanucleotide repeat expansions with hundreds to thousands of repeats.
Interpretation
All detected variants are evaluated according to American College of Medical Genetics and Genomics recommendations.(1) Variants are classified based on known, predicted, or possible pathogenicity and reported with interpretive comments detailing their potential or known significance.
Clinical Reference
1. Richards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405-424
2. Graff-Radford NR, Woodruff BK. Frontotemporal dementia. Semin Neurol. 2007;27(1):48-57
3. Karch CM, Wen N, Fan CC, et al. Selective genetic overlap between amyotrophic lateral sclerosis and diseases of the frontotemporal dementia spectrum. JAMA Neurol. 2018;75(7):860-875
Day(s) Performed
Varies
Report Available
21 to 28 daysTest 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
81403
81406 x 10
81404 x 3
81405 x 2
81407
81479
81479 (if appropriate for government payers)
LOINC Code Information
| Test ID | Test Order Name | Order LOINC Value |
|---|---|---|
| AFTDP | FTD and ALS Gene Panel | 51966-0 |
| Result ID | Test Result Name | Result LOINC Value |
|---|---|---|
| 617494 | Test Description | 62364-5 |
| 617495 | Specimen | 31208-2 |
| 617496 | Source | 31208-2 |
| 617497 | Result Summary | 50397-9 |
| 617498 | Result | 82939-0 |
| 617499 | Interpretation | 69047-9 |
| 618174 | Additional Results | 82939-0 |
| 617500 | Resources | 99622-3 |
| 617501 | Additional Information | 48767-8 |
| 617502 | Method | 85069-3 |
| 617503 | Genes Analyzed | 48018-6 |
| 617504 | Disclaimer | 62364-5 |
| 617505 | Released By | 18771-6 |
Testing Algorithm
For more information see Inherited Motor Neuron Disease and Dementia Testing Algorithm
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