Alzheimer's Disease, Familial via the PSEN1 Gene
Summary and Pricing 
Test Method
Sequencing and CNV Detection via NextGen Sequencing using PG-Select Capture Probes| Test Code | Test Copy Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 6921 | PSEN1 | 81405 | 81405,81479 | $990 | Order Options and Pricing |
Pricing Comments
Testing run on PG-select capture probes includes CNV analysis for the gene(s) on the panel but does not permit the optional add on of exome-wide CNV analysis. Any of the NGS platforms allow reflex to other clinically relevant genes, up to whole exome or whole genome sequencing depending upon the base platform selected for the initial test.
An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.
This test is also offered via a custom panel (click here) on our exome or genome backbone which permits the optional add on of exome-wide CNV or genome-wide SV analysis.
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.
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.
Genetics
FAD is inherited in an autosomal dominant manner and can be caused by mutations in the PSEN1 gene. Most causative PSEN1 variants are missense mutations distributed throughout the gene, though frameshift mutations, splice site mutations and large deletions in PSEN1 have also been identified in FAD patients (Rogaeva et al. 2001; Janssen et al. 2003).
PSEN1 encodes the presenilin-1 (PS1) protein. PS1 is the catalytic 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). PSEN1 mutations are believed to act in a dominant negative manner to interfere with wildtype PS1 activity and to cause FAD via impaired APP processing by gamma-secretase (Nornes et al. 2007; Heilig et al. 2013).
Clinical Sensitivity - Sequencing with CNV PG-Select
In a study of patients with Alzheimer's disease ~11% (48 of 414) had PSEN1 mutations. Of these, 80% had age of onset PSEN1 mutations in FAD cases to be ~50% (32/56 and 16/31) (Wallon et al. 2012; Janssen et al. 2003).
Testing Strategy
This test provides full coverage of all coding exons of the PSEN1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
PSEN1 testing should be considered for individuals with early onset dementia who have at least one affected family member. PSEN1 testing can also determine carrier status of individuals for a known familial mutation.
PSEN1 testing should be considered for individuals with early onset dementia who have at least one affected family member. PSEN1 testing can also determine carrier status of individuals for a known familial mutation.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| PSEN1 | 104311 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Diseases
| Name | Inheritance | OMIM ID |
|---|---|---|
| Alzheimer's Disease, Type 3 | AD | 607822 |
| Frontotemporal Dementia | AD | 600274 |
Related Tests
| Name |
|---|
| Alzheimer's Disease, Familial, Panel |
| Frontotemporal Dementia via the MAPT Gene |
Citations
- Heilig EA, Gutti U, Tai T, Shen J, Kelleher RJ. 2013. Trans-Dominant Negative Effects of Pathogenic PSEN1 Mutations on -Secretase Activity and A Production. Journal of Neuroscience 33: 11606–11617. PubMed ID: 23843529
- Janssen JC. et al. 2003. Neurology. 60: 235-9 PubMed ID: 12552037
- Kumar-Singh S. et al. 2000. Human Molecular Genetics. 9: 2589-98. PubMed ID: 11063718
- Nornes S, Newman M, Verdile G, Wells S, Stoick-Cooper CL, Tucker B, Frederich-Sleptsova I, Martins R, Lardelli M. 2007. Interference with splicing of Presenilin transcripts has potent dominant negative effects on Presenilin activity. Human Molecular Genetics 17: 402–412. PubMed ID: 17981814
- Rogaeva EA, Fafel KC, Song YQ, Medeiros H, Sato C, Liang Y, Richard E, Rogaev EI, Frommelt P, Sadovnick AD, Meschino W, Rockwood K, et al. 2001. Screening for PS1 mutations in a referral-based series of AD cases: 21 Novel mutations. Neurology 57: 621–625. PubMed ID: 11524469
- 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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