Dementia Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10309 APP 81406,81479 Order Options and Pricing
C9orf72 81479,81479
CHCHD10 81479,81479
CHMP2B 81479,81479
CSF1R 81479,81479
DCTN1 81479,81479
FUS 81406,81479
GRN 81406,81479
ITM2B 81479,81479
MAPT 81406,81479
PSEN1 81405,81479
PSEN2 81406,81479
SQSTM1 81479,81479
TARDBP 81405,81479
TBK1 81479,81479
TREM2 81479,81479
UBQLN2 81479,81479
VCP 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10309Genes x (18)81479 81405, 81406, 81479 $890 Order Options and Pricing

Pricing Comments

$250 for C9orf72 repeat expansion only (see test #151).

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our PGxome Custom Panel tool.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

For Reflex to PGxome pricing click here.

Turnaround Time

C9orf72 assays completed within 12 days on average for standard orders. Reflexive panels are completed within an additional 18 days on average for standard orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.

EMAIL CONTACTS

Genetic Counselors

Geneticist

Clinical Features and Genetics

Clinical Features

Dementia is characterized by cognitive and behavioral decline. It is caused by a progressive degeneration and atrophy of various regions of the brain. Progressive dementia is common in several neurodegenerative syndromes in adults. The most prevalent forms are Alzheimer’s disease (AD) and Frontotemporal dementia (FTD) (Wu et al. 2012. PubMed ID: 22728850; Onyike and Diehl-Schmid 2013. PubMed ID: 23611343). Although there is a considerable phenotypic overlap between AD and FTD, several distinguishing features exist.

AD may be distinguished by a later age of onset and slower progression compared to FTD. In addition, memory loss and visual and spatial abnormalities are the chief complaints in AD; while behavioral abnormalities are the main features in FTD. Patients with FTD often develop motor abnormalities, which are rare in patients with AD (Harciarek and Jodzia. 2005. PubMed ID: 16328732).

Based on the age of onset of symptoms, AD is conventionally classified in two types: early-onset AD when symptoms begin before the age of 65 years, and late-onset AD when symptoms begin after the age of 65 years. Age of onset may differ among affected relatives (Brickell et al. 2006. PubMed ID: 16966510). Gross cortical atrophy accompanied by aggregation of beta-amyloid protein in the form of plaques and tangles are hallmark features of the disease (Blennow et al. 2006. PubMed ID: 16876668). The dysfunction of the affected areas of the brain results in gradual deterioration of memory that affects language, personality, and cognitive control. Symptoms include irritability, aggression, confusion and mood changes. As the disease progresses, additional symptoms develop and include sleep disturbances, loss of language skills, depression, and withdrawal. Eventually, patients do not recognize the faces of close family members and lose the ability to perform routine tasks independently (Bäckman et al. 2004. PubMed ID: 15324363).

FTD, previously referred to as Pick’s disease, is a clinically heterogeneous syndrome due to the progressive degeneration and atrophy of various regions of the frontal and temporal lobes of the brain. Frontal temporal dementias account for about 10% of all dementias. Symptoms are insidious and begin usually during the fourth and sixth decades of life; although earlier and later onsets have been documented (Snowden et al. 2002. PubMed ID: 11823324; Bruni et al. 2007. PubMed ID: 17620546). The annual incidence of FTD is 3-4 per 100,000 (Onyike and Diehl-Schmid 2013. PubMed ID: 23611343).

Two major forms, the behavioral-variant (FTD-bv) and the primary progressive aphasia (PPA), are recognized based on the site of onset of degeneration and the associated symptoms. FTD-bv comprises about half of FTD cases with the degenerative process beginning in the frontal lobes and resulting in personality changes and deterioration of social conducts. Most common behavioral changes are: disinhibition, apathy, deterioration of executive function, obsessive thoughts, compulsive behavior, and neglect of personal hygiene (Rascovsky et al. 2011. PubMed ID: 21810890). PPA is a language disorder that is further divided into two sub-forms: progressive nonfluent PPA and semantic variant PPA. Nonfluent PPA is characterized by difficulty in verbal communications, word retrieval, and speech distortion. Reading, writing and spelling are also affected; while memory is relatively preserved. Semantic variant PPA is characterized by the progressive impairment of word comprehension, object and face recognition, and loss of semantic memory. Reading and writing skills are relatively preserved (Gustafson. 1993. PubMed ID: 8401782).

Genetics

Early-onset AD accounts for less than 2% of AD cases and is inherited in an autosomal dominant manner. In late-onset AD, disease and genetic etiology is unclear. Highly penetrant pathogenic variants in the PSEN1, APP, and PSEN2 genes account for up to 70%, 15% and 5% of early-onset AD cases (Bird. 2018. PubMed ID: 20301340). The majority of pathogenic variants in the PSEN1 gene are missense changes; however loss of function variants, including gross deletions, have been reported in a few cases (Evin et al. 2002. PubMed ID: 11997713). The c.839A>C (p.Glu280Ala) and c.617G>C (p.Gly206Ala) changes have been previously described as founder variants in Columbian and Caribbean Hispanics, respectively (Lalli et al. 2014. PubMed ID: 24239249; Lee et al. 2014. PubMed ID: 25333068). Missense changes in exons 16 and 17 resulting in disruption of APP processing into mature amyloid-beta protein represent ~60% of pathogenic variants in the APP gene whereas gross duplications of the APP gene account for about ~30% cases (Wallon et al. 2012. PubMed ID: 22475797; Rovelet-Lecrux et al. 2006. PubMed ID: 16369530). Missense changes primarily in exons 6 and 8 are the account for over half of the pathogenic variants found in the PSEN2 gene. The c.422A>T (p.Asn141Ile) change has been reported as a founder variant in Germany (Yu et al. 2010. PubMed ID: 20457965).

FTDs are inherited in 30-50% of cases in an autosomal dominant manner with pathogenic variants in C9orf72, MAPT and GRN accounting for about 30%, 15% and 25% of these cases respectively. An expansion of a GGGGCC hexanucleotide repeat in an intron 1 non-coding region of the C9orf72 gene is the most common cause of FTD. Greater than 30 hexanucleotide repeats is considered pathogenic whereas less than 25 repeats is considered benign (Majounie et al. 2012. PubMed ID: 22406228; van der Zee et al. 2013. PubMed ID: 23111906). Missense changes in exons 2 and 9-13 are the most common pathogenic variants in the MAPT gene. However, spice site alterations, gross duplications and inframe deletions/insertions have also been reported (Goldman and Van Deerlin et al. 2018. PubMed ID: 29971646). Several different types of pathogenic variants including missense, nonsense, splicing and small insertions/deletions have been reported throughout the GRN gene. Gross deletions account for ~1.5% GRN-FTD cases (Hsiung and Feldman. 2020. PubMed ID: 20301545).

Pathogenic variants in the CHCHD10, CHMP2B, CSF1R, FUS, ITM2B, SQSTM1, TARDBP, TBK1, TREM2 and VCP genes have also been associated with autosomal dominant ALS but represent less than 5% of cases (Goldman and Van Deerlin et al. 2018. PubMed ID: 29971646). Pathogenic variants in the UBQLN2 gene are associated with X-linked disease (Siddique and Siddique. 2019. PubMed ID: 20301623). Pathogenic variants in the DCTN1 gene are associated with autosomal dominant Perry syndrome.

See individual gene summaries for more information about molecular biology of gene products and spectra of pathogenic variants. 

Clinical Sensitivity - Sequencing with CNV PGxome

In ~95% of early onset AD cases, pathogenic variants in the PSEN1, PSEN2, and APP genes are detected (Bird. 2018. PubMed ID: 20301340). In familial FTD cases, pathogenic variants are identified in up to 65% of total cases with C9orf72, MAPT, and GRN accounting for about 75% of the positive cases (Goldman and Van Deerlin et al. 2018. PubMed ID: 29971646). The majority of genes in this panel have no or very few large deletions/duplications.

Testing Strategy

The C9orf72 hexanucleotide repeat expansion test will be performed first as this is the most common cause of ALS and FTD. If C9orf72 testing is negative then the sequencing panel will be performed. Results for the C9orf72 repeat expansion and sequencing panel will be reported separately. Concurrent testing is available upon request.

The C9orf72 repeat expansion tests each utilize four unique assays: (1) a repeat primed PCR assay with the locus specific primer 5’ (upstream) of the repeat region (2) a repeat primed PCR assay with the locus specific primer 3’ (downstream) of the repeat region and (3,4) two unique fluorescent fragment length assays.

The sequencing panel typically provides 99.9% coverage of all coding exons of the genes listed plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

Indications for Test

Candidates for AD testing include patients presenting with early-onset disease, a positive family history, and cardinal symptoms including memory impairment, impaired executive function and behavioral and/or psychological symptoms (Bird. 2018. PubMed ID: 20301340).

The International Behavioral Variant FTD Criteria Consortium (FTDC) defines diagnosis for bvFTD as patients that present with three of the six clinical features: disinhibition, apathy, loss of sympathy, compulsive behaviors, hyperorality, and/or dysexecutive neuropsychologic profile. Diagnosis for PPA includes language deficits as the primary cause of impaired living and aphasia being most prominent at symptom onset.

Genes

Official Gene Symbol OMIM ID
APP 104760
C9orf72 614260
CHCHD10 615903
CHMP2B 609512
CSF1R 164770
DCTN1 601143
FUS 137070
GRN 138945
ITM2B 603904
MAPT 157140
PSEN1 104311
PSEN2 600759
SQSTM1 601530
TARDBP 605078
TBK1 604834
TREM2 605086
UBQLN2 300264
VCP 601023
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®
Alzheimer Disease, Familial, Panel

Citations

  • B├Ąckman et al. 2004. PubMed ID: 15324363
  • Bird. 2018. PubMed ID: 20301340
  • Blennow et al. 2006. PubMed ID: 16876668
  • Brickell et al. 2006. PubMed ID: 16966510
  • Bruni et al. 2007. PubMed ID: 17620546
  • Evin et al. 2002. PubMed ID: 11997713
  • Goldman and Van Deerlin 2018. PubMed ID: 29971646
  • Gustafson L. 1993. PubMed ID: 8401782
  • Harciarek and Jodzio. 2005. PubMed ID: 16328732
  • Hsiung and Feldman, 2020. PubMed ID: 20301545
  • Lalli et al. 2014. PubMed ID: 24239249
  • Lee et al. 2014. PubMed ID: 25333068
  • Majounie et al. 2012. PubMed ID: 22406228
  • Onyike and Diehl-Schmid. 2013. PubMed ID: 23611343
  • Rascovsky et al. 2011. PubMed ID: 21810890
  • Rovelet-Lecrux et al. 2006. PubMed ID: 16369530
  • Siddique and Siddique. 2019. PubMed ID: 20301623
  • Snowden et al. 2002. PubMed ID: 11823324
  • van der Zee et al. 2013. PubMed ID: 23111906
  • Wallon et al. 2012. PubMed ID: 22475797
  • Wu et al. 2012. PubMed ID: 22728850
  • Yu et al. 2010. PubMed ID: 20457965

Ordering/Specimens

Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Type


2) Select Additional Test Options

STAT and Prenatal Test Options are not available with Patient Plus.

No Additional Test Options are available for this test.

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