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Alzheimer's Disease, Familial via the PSEN2 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
6923 PSEN2 81406 81406,81479 $990 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
6923PSEN281406 81406,81479 $990 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.

Testing run on PG-Select capture probes does not include exome-wide CNV analysis. Reflex is available to PGxome or an exome-based panel, or you can use this gene list to create a custom panel (click here).

Click here for costs to reflex to whole PGxome.

Turnaround Time

3 weeks on average for standard orders or 2 weeks 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

  • Li Fan, MD, PhD, FCCMG, FACMG

Clinical Features and Genetics

Clinical Features

Familial Alzheimer's disease (FAD) is a neurodegenerative disorder characterized by onset of dementia before 60 years of age. Dementia initially presents in FAD patients as short term memory problems or disorientation between 30 and 60 years of age. Cognitive decline is observed over the next 10-20 years with apraxia, progressive memory loss and impaired spatial skills being common presentations (Wallon et al. 2012). Motor disturbances such as cerebellar ataxia and spastic paraparesis are also observed in a subset of patients. The key neuropathology of FAD includes: amyloid plaques, neurofibrillary tangles, neuronal loss and brain atrophy (Wu et al. 2012). An important feature of the FAD diagnosis is that an individual has at least one affected family member. Patients with FAD caused by PSEN2 mutations typically show a later age of onset in the 50s or 60s as compared to onset in the 30s or 40s as seen in FAD caused by APP or PSEN1 variants (Jayadev et al. 2010). In addition, PSEN2-related FAD patients have a higher frequency of behavioral and psychotic symptoms of dementia (BPSD), such as hallucinations or delusions (Canevelli et al. 2014).

Genetics

FAD is inherited in an autosomal dominant manner and can be caused by mutations in the PSEN2 gene. Most causative PSEN2 variants are missense variants distributed throughout the gene. Two variants, N141I and M239V, account for 74% of all PSEN2-related FAD cases (Canevelli et al. 2014).

PSEN2 encodes the presenilin-2 (PS2) protein. PS2 is a subunit of the gamma-secretase complex which cleaves the Alzheimer's-associated alpha-beta precursor protein (APP). APP undergoes sequential processing to produce two amyloid-beta isoforms: AB40 and AB42. Accumulation of characteristic amyloid-beta plaques in FAD patients are associated with improperly processed APP, specifically increased ratios of the AB42 isoform relative to AB40 (Kumar-Singh et al. 2000). Although PSEN2 knockout mice do not show amyloid-beta processing defects, pathogenic PSEN2 variants were shown to alter AB40:AB42 ratios in in vitro cell-based assays (Herreman et al. 1999; Walker et al. 2005).

Clinical Sensitivity - Sequencing with CNV PG-Select

PSEN2 variants only account for a small percent of FAD cases, with pathogenic PSEN2 variants identified in 0.4-10% of cases of FAD or early onset dementia (Finckh et al. 2000; Janssen et al. 2003; Guerreiro et al. 2010).

Testing Strategy

This test provides full coverage of all coding exons of the PSEN2 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

PSEN2 testing should be considered for individuals with early onset dementia who have at least one affected family member, especially if they present with delusions or hallucinations. PSEN2 testing can also determine carrier status of individuals for a known familial mutation.

Gene

Official Gene Symbol OMIM ID
PSEN2 600759
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Alzheimer's Disease, Type 4 AD 606889

Related Test

Name
Alzheimer's Disease, Familial, Panel

Citations

  • Canevelli M, Piscopo P, Talarico G, Vanacore N, Blasimme A, Crestini A, Tosto G, Troili F, Lenzi GL, Confaloni A, Bruno G. 2014. Familial Alzheimer’s disease sustained by presenilin 2 mutations: Systematic review of literature and genotype–phenotype correlation. Neuroscience & Biobehavioral Reviews 42: 170–179. PubMed ID: 24594196
  • Finckh U, Müller-Thomsen T, Mann U, Eggers C, Marksteiner J, Meins W, Binetti G, Alberici A, Hock C, Nitsch RM, others. 2000. High prevalence of pathogenic mutations in patients with early-onset dementia detected by sequence analyses of four different genes. The American Journal of Human Genetics 66: 110–117. PubMed ID: 10631141
  • Guerreiro RJ, Baquero M, Blesa R, Boada M, Brás JM, Bullido MJ, Calado A, Crook R, Ferreira C, Frank A, Gómez-Isla T, Hernández I, et al. 2010. Genetic screening of Alzheimer’s disease genes in Iberian and African samples yields novel mutations in presenilins and APP. Neurobiology of Aging 31: 725–731. PubMed ID: 18667258
  • Herreman A, Hartmann D, Annaert W, Saftig P, Craessaerts K, Serneels L, Umans L, Schrijvers V, Checler F, Vanderstichele H, others. 1999. Presenilin 2 deficiency causes a mild pulmonary phenotype and no changes in amyloid precursor protein processing but enhances the embryonic lethal phenotype of presenilin 1 deficiency. Proceedings of the National Academy of Sciences 96: 11872–11877. PubMed ID: 10518543
  • Janssen JC. et al. 2003. Neurology. 60: 235-9 PubMed ID: 12552037
  • Jayadev S, Leverenz JB, Steinbart E, Stahl J, Klunk W, Yu CE, Bird TD. 2010. Alzheimer’s disease phenotypes and genotypes associated with mutations in presenilin 2. Brain 133: 1143–1154. PubMed ID: 23952003
  • Kumar-Singh S. et al. 2000. Human Molecular Genetics. 9: 2589-98. PubMed ID: 11063718
  • Walker ES, Martinez M, Brunkan AL, Goate A. 2005. Presenilin 2 familial Alzheimer’s disease mutations result in partial loss of function and dramatic changes in Abeta 42/40 ratios. Journal of Neurochemistry 92: 294–301. PubMed ID: 15663477
  • Wallon D. et al. 2012. Journal of Alzheimer's Disease. 30: 847–856 PubMed ID: 22475797
  • Wu L. et al. 2012. The Canadian Journal of Neurological Sciences. 39: 436–445 PubMed ID: 22728850

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

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.


Specimen Types

Specimen Requirements and Shipping Details

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ORDER OPTIONS

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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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