Frontotemporal Dementia via the MAPT Gene

Summary and Pricing

Test Method

Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
3491 MAPT 81406 81406,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3491MAPT81406 81406(x1), 81479(x1) $640 Order Options and Pricing

Pricing Comments

This test is also offered via our exome backbone with CNV detection (click here). The exome-based test may be higher priced, but permits reflex to the entire exome or to any other set of clinically relevant genes.

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

Turnaround Time

18 days on average for standard orders or 13 days on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn 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

  • Luke Drury, PhD

Clinical Features and Genetics

Clinical Features

Frontotemporal dementia (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. Symptoms are insidious and begin usually during the fourth and sixth decades of life; although earlier and later onset have been documented (Snowden et al. 2002; Bruni et al. 2007).

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.

In FTD-bv the degenerative process begins in the frontal lobes and results 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.

In PPA the degenerative process begins in the temporal lobes. PPA is a language disorder that is further divided into two sub-forms: progressive non-fluent aphasia (PNFA) and 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 is relatively preserved. SD 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 et al. 1993).

The clinical diagnosis of FTD is based on the combination of medical history, physical and neurological examination, brain imaging, and neuropsychological and psychiatric assessment (Neary et al. 1998; Snowden 2002; Rascovsky et al 2011; Mesulam 2001).

FTD affects people worldwide, with a prevalence of up to 15 per 100,000 (Ratnavalli et al. 2002). It is the second most common dementia in people under the age of 65 years, after Alzheimer's disease, accounting for up to 20% of presenile dementia cases (Snowden et al. 2002).

Genetics

FTD is inherited in about 40% of cases (Rosso et al. 2003). About 10% of these families have a history of dementia or a related condition that is inherited in an autosomal dominant manner. Because several symptoms of FTD overlap with symptoms of other psychiatric disorders, and because of incomplete family history, the mode of transmission of FTD could not be established in most families (Pickering-Brown et al. 2008; Rohrer et al. 2009).

FTD is genetically heterogeneous. Several genes have been implicated in the disorder: C9orf72, GRN, MAPT, CHMPEB, TARDBP, FUS and VCP.

Pathogenic variants in the MAPT gene account for up to 9% of patients with a clinical diagnosis of FTD (Pickering-Brown et al. 2008; Rohrer et al. 2009). About 70 different MAPT pathogenic variants have been reported in patients with the various forms of FTD. They include both missense and truncating variants and are usually classified in two categories. The first category includes missense variants and small deletions in the coding region of the gene; they affect the ability of the tau protein to associate with microtubules. The second category includes splicing variants, missense and silence variants, which affect the alternative splicing of exon 10. This results in the alteration of the isoform ratio and the development of FTD (Hutton et al. 1998; Spillantini et al. 1998). Large pathogenic copy number variations appear to be a rare cause of FTD. To date, only one large deletion has been reported (Human Gene Mutation Database; Rovelet-Lecrux et al. 2009).

In addition to FTD, MAPT pathogenic variants were reported in patients with progressive supranuclear palsy (Ros et al. 2005).

The MAPT gene encodes microtubule-associated protein tau. Through alternative splicing, the primary transcript produces six different isoforms that are differentially expressed during development and appear to have differential physiological roles (D’Souza et al. 2005).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the MAPT gene account for up to 9% of patients with a clinical diagnosis of frontotemporal dementia (Pickering-Brown et al. 2008; Rohrer et al. 2009).

Testing Strategy

This test provides full coverage of all coding exons of the MAPT gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

All patients with symptoms and MRI findings suggestive of FTD-bv or PPA (Neary et al. 1998; Snowden 2002; Rascovsky et al. 2011; Mesulam 2001).

Gene

Official Gene Symbol OMIM ID
MAPT 157140
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Tests

Name
Alzheimer's Disease, Familial via the PSEN1 Gene
Frontotemporal Dementia via the GRN Gene

Citations

  • Bruni A.C. et al. 2007. Neurology. 69: 140-7. PubMed ID: 17620546
  • Gustafson L. 1993. Dementia. 4: 143-8. PubMed ID: 8401782
  • Human Gene Mutation Database (Bio-base).
  • Hutton M. et al. 1998. Nature. 393: 702-5. PubMed ID: 9641683
  • Mesulam M.M. 2001. Primary progressive aphasia. Ann. Neurol. 49: 425–432. PubMed ID: 11310619
  • Neary D. et al. 1998. Neurology. 51: 1546-54. PubMed ID: 9855500
  • Pickering-Brown S.M. et al. 2008. Brain. 131: 721-31. PubMed ID: 18192287
  • Rascovsky K. et al. 2011. Brain : a Journal of Neurology. 134: 2456-77. PubMed ID: 21810890
  • Ratnavalli E. et al. 2002. Neurology. 58: 1615-21. PubMed ID: 12058088
  • Rohrer J.D. et al. 2009. Neurology. 73: 1451-6. PubMed ID: 19884572
  • Ros R. et al. 2005. Archives of Neurology. 62: 1444-50. PubMed ID: 16157753
  • Rosso S.M. et al. 2003. Brain. 126: 2016-22. PubMed ID: 12876142
  • Rovelet-Lecrux A. et al. 2009. Human Mutation. 30: E591-E602. PubMed ID: 19263483
  • Snowden J.S. 2002. The British Journal of Psychiatry 180: 140-3. PubMed ID: 11823324
  • Spillantini M.G. et al. 1998. Proceedings of the National Academy of Sciences of the United States of America. 95: 7737-41. PubMed ID: 9636220

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.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

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

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1) Select Test Method (Backbone)


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2) Select Additional Test Options

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

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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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