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  • Test code: 03505
  • Turnaround time:
    10–21 calendar days (14 days on average)
  • Preferred specimen:
    3mL whole blood in a purple-top tube
  • Alternate specimens:
    DNA or saliva/assisted saliva
  • Sample requirements
  • Request a sample kit
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Invitae Frontotemporal Dementia Panel

Test description

The Invitae Frontotemporal Dementia Panel analyzes up to 13 genes associated with frontotemporal dementia (FTD), a neurodegenerative disorder characterized by progressive behavioral and cognitive impairment. The genes on the Invitae Frontotemporal Dementia Panel were curated based on the available evidence to date in order to provide analysis for a number of newly characterized FTD genes along with well-known genetic causes of FTD, with the exception of the C9orf72 gene, which is not included in this panel and is thought to be the most common genetic cause of both FTD and ALS. C9orf72 hexanucleotide repeat expansion testing is considered first-line genetic testing for individuals with a personal and/or family history of FTD and/or ALS. The Invitae Frontotemporal Dementia Panel should only be considered in individuals who have previously had negative C9orf72 testing.

Individuals with a clinical diagnosis of FTD, especially those with a family history of FTD and/or ALS, may benefit from diagnostic genetic testing. Identification of the molecular basis of FTD in an affected individual may help to confirm a suspected diagnosis, provide anticipatory guidance, determine which relatives may be at risk, and/or promote enrollment in clinical trials.

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Primary panel (9 genes)

CHCHD10 DCTN1 FUS GRN MAPT TARDBP TBK1 UBQLN2 VCP

Add-on Preliminary-evidence Genes for Frontotemporal Dementia (4 genes)

The CHMP2B, HNRNPA2B1, PSEN1, and SQSTM1 genes currently have early evidence of a clinical association with frontotemporal dementia. Some clinicians may wish to include genes which do not currently have a definitive clinical association, but which may prove to be clinically significant in the future. These genes can be added at no additional charge. Visit our Preliminary-evidence genes page to learn more.

CHMP2B HNRNPA2B1 PSEN1 SQSTM1

Alternative tests to consider

For a broader analysis of the genetics of hereditary dementia and ALS:

Clinicians may also consider the Invitae Hereditary Parkinson’s Disease and Parkinsonism panel for individuals with a personal or family history of Parkinson’s disease or parkinsonian features.

Frontotemporal dementia (FTD) is a neurodegenerative disorder characterized by progressive behavioral and cognitive impairment due to atrophy of the frontal and/or anterior temporal lobes of the brain. Age of onset is variable but most commonly occurs between the 40s and 60s. It is one of the most common types of dementia in individuals under the age of 65. The most common form of FTD is behavioral variant FTD (bvFTD), which is characterized by degeneration that begins in the frontal lobes of the brain, resulting in behavioral and personality changes including apathy, restlessness, disinhibition, compulsive behaviors, and hyperorality. Individuals often display a marked lack of insight into their symptoms. A subset of individuals present with language impairment caused by degeneration in the temporal lobes of the brain, categorized broadly as primary progressive aphasia, which can be further delineated as progressive nonfluent variant aphasia (PNFA) or semantic dementia (SD). PNFA is characterized by difficulty in verbal communications, word retrieval, and speech distortion. Reading, writing and spelling are also affected, while memory remains relatively intact. SD is characterized by progressive impairment of word comprehension, object and face recognition, and loss of semantic memory. Reading and writing skills are typically preserved. Other features of FTD may include stereotypies, mutism, and dystonia. Some affected individuals also develop features of motor neuron disease such as ALS or a movement disorder such as parkinsonism. Approximately 40% of FTD has a hereditary cause.

GeneInheritanceAssociated neurological disordersProportion of FTD
Autosomal dominantX-linked
CHCHD10 FTDALS2; Spinal muscular atrophy; Mitochondrial myopathy Rare
CHMP2B* FTD3; ALS17 Unknown
DCTN1 Perry Syndrome, which may present with features of ALS and/or FTD ~100% of Perry Syndrome, rare cause of isolated ALS/FTD
FUS ALS6 ~4% of familial ALS and approximately 1% of sporadic ALS with or without FTD
GRN FTD with TDP43 inclusions 13-25%
HNRNPA2B1* Inclusion body myopathy with early-onset Paget disease with or without FTD 2 (IBMPFD2) Unknown
MAPT FTD with or without parkinsonism; Pick disease 15-20%
PSEN1* Alzheimer’s disease 3 (AD3); Pick disease; FTD; Dilated cardiomyopathy Unknown
SQSTM1* FTDALS3; Paget disease of bone Unknown
TARDBP ALS10; FTD with TDP43 inclusions ~4% of familial ALS and ~1% of sporadic ALS with or without FTD
TBK1 FTDALS4 1-4% of hereditary FTD and/or ALS
UBQLN2 ALS15 Rare
VCP Inclusion Body Myopathy with Paget Disease of Bone and/or Frontotemporal Dementia (IBMPFD); ALS14 ~100% of individuals who meet diagnostic criteria for IBMPFD, ~1-2% of familial ALS with or without FTD

*Preliminary-evidence gene

The clinical sensitivity of this panel is dependent on the patient’s true clinical diagnosis, which can often only be accurately determined upon autopsy. For each gene, the table in the Clinical description section above shows the percentage of clinical cases in which a pathogenic variant is expected. For some genes, the incidence is rare and the clinical sensitivity is unknown. The sensitivity of this test also depends on age of onset and family history.

It is important to note that pathogenic variants in the C9orf72 gene account for an estimated 25% of familial ALS, and this panel should only be considered in those who have already been tested for C9orf72 at an alternate laboratory.

The majority of hereditary forms of FTD are inherited in an autosomal dominant manner. The UBQLN2 gene is associated with X-linked ALS with or without FTD.

Hereditary FTD is associated with variable expressivity and age of onset, and penetrance is typically age-dependent and difficult to calculate for the majority of genes. Symptom expressivity varies even within families for the majority of genetic forms of FTD. Penetrance of GRN-related FTD has an estimated penetrance of 90% by 75 years of age. Reduced penetrance has been described for MAPT-related FTD.

The overall annual incidence of FTD has been estimated at 3.5 cases per 100,000 individuals aged 45-64 years. It is estimated that approximately 40% of all people with FTD have a hereditary form of the condition.

A genetic cause for FTD may be suspected in individuals who have:

  • A clinical diagnosis of frontotemporal dementia and/or ALS, and who have previously tested negative for repeat expansion of the C9orf72 gene
  • A clinical diagnosis of early-onset frontotemporal dementia (onset before 60 years of age), especially in those with a family history of dementia or ALS
  • No personal history of disease (unaffected individuals), but who are known to be at risk for a hereditary form of FTD because of family history

In addition to meeting one of the above criteria, individuals considering genetic testing for hereditary forms of FTD should first receive thorough pre-test genetic counseling from a professional qualified to provide such counseling regarding the implications of testing for neurodegenerative disorders that have no known treatment or cure at this time.

  1. Woollacott, IO, Rohrer, JD. The clinical spectrum of sporadic and familial forms of frontotemporal dementia. J. Neurochem. 2016; :None. PMID: 27144467
  2. Isaacs, AM, et al. Frontotemporal dementia caused by CHMP2B mutations. Curr Alzheimer Res. 2011; 8(3):246-51. PMID: 21222599
  3. Seelaar, H, et al. Distinct genetic forms of frontotemporal dementia. Neurology. 2008; 71(16):1220-6. PMID: 18703462
  4. Gómez-Tortosa, E, et al. C9ORF72 hexanucleotide expansions of 20-22 repeats are associated with frontotemporal deterioration. Neurology. 2013; 80(4):366-70. PMID: 23284068
  5. Seelen, M, et al. No mutations in hnRNPA1 and hnRNPA2B1 in Dutch patients with amyotrophic lateral sclerosis, frontotemporal dementia, and inclusion body myopathy. Neurobiol. Aging. 2014; 35(8):1956.e9-1956.e11. PMID: 24612671
  6. Mercy, L, et al. Incidence of early-onset dementias in Cambridgeshire, United Kingdom. Neurology. 2008; 71(19):1496-9. PMID: 18981371
  7. Cruts, M, et al. C9orf72-Related Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. 2015 Jan 08. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 25577942
  8. Hsiung, GYR, Feldman, HH. GRN-Related Frontotemporal Dementia. 2007 Sep 07. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301545
  9. van, Swieten, JC, et al. MAPT-Related Disorders. 2000 Nov 07. In: Pagon, RA, et al, editors. GeneReviews(®) (Internet). University of Washington, Seattle. PMID: 20301678
  10. Van, Deerlin, VM, et al. Common variants at 7p21 are associated with frontotemporal lobar degeneration with TDP-43 inclusions. Nat. Genet. 2010; 42(3):234-9. PMID: 20154673
  11. Bang, J, et al. Frontotemporal dementia. Lancet. 2015; 386(10004):1672-82. PMID: 26595641
  12. Goldman, JS, et al. Genetic counseling and testing for Alzheimer disease: joint practice guidelines of the American College of Medical Genetics and the National Society of Genetic Counselors. Genet. Med. 2011; 13(6):597-605. PMID: 21577118
  13. Renton, AE, et al. State of play in amyotrophic lateral sclerosis genetics. Nat. Neurosci. 2014; 17(1):17-23. PMID: 24369373
  14. Roggenbuck, J, et al. Genetic testing and genetic counseling for amyotrophic lateral sclerosis: an update for clinicians. Genet. Med. 2016; :None. PMID: 27537704

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence in the transcript listed below. In addition, analysis covers the select non-coding variants specifically defined in the table below. Any variants that fall outside these regions are not analyzed. Any specific limitations in the analysis of these genes are also listed in the table below.

Based on validation study results, this assay achieves >99% analytical sensitivity and specificity for single nucleotide variants, insertions and deletions <15bp in length, and exon-level deletions and duplications. Invitae's methods also detect insertions and deletions larger than 15bp but smaller than a full exon but sensitivity for these may be marginally reduced. Invitae’s deletion/duplication analysis determines copy number at a single exon resolution at virtually all targeted exons. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. Certain types of variants, such as structural rearrangements (e.g. inversions, gene conversion events, translocations, etc.) or variants embedded in sequence with complex architecture (e.g. short tandem repeats or segmental duplications), may not be detected. Additionally, it may not be possible to fully resolve certain details about variants, such as mosaicism, phasing, or mapping ambiguity. Unless explicitly guaranteed, sequence changes in the promoter, non-coding exons, and other non-coding regions are not covered by this assay. Please consult the test definition on our website for details regarding regions or types of variants that are covered or excluded for this test. This report reflects the analysis of an extracted genomic DNA sample. In very rare cases, (circulating hematolymphoid neoplasm, bone marrow transplant, recent blood transfusion) the analyzed DNA may not represent the patient's constitutional genome.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
CHCHD10 NM_213720.2
CHMP2B NM_014043.3
DCTN1 NM_004082.4
FUS NM_004960.3
GRN NM_002087.3
HNRNPA2B1 NM_031243.2
MAPT NM_005910.5
PSEN1 NM_000021.3
SQSTM1 NM_003900.4
TARDBP NM_007375.3
TBK1 NM_013254.3
UBQLN2 NM_013444.3
VCP NM_007126.3