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Alexander Disease via the GFAP Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8231 GFAP 81405 81405,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8231GFAP81405 81405,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

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

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • Maxime Cadieux-Dion, PhD

Clinical Features and Genetics

Clinical Features

Alexander disease is a rare, and often fatal, disorder affecting the midbrain and cerebellum of the central nervous system. Based on age of onset, different forms of Alexander disease have been described: infantile, juvenile, and adult forms. Generally, earlier onset is associated with more severe and rapid disease course (Srivastava et al. 2002).

The infantile form is the most common form of Alexander disease. Typically, this form begins before age 2 with progressive psychomotor retardation and loss of developmental milestones. Some patients also show hyperreflexia and ataxia. Survival ranges from several weeks to several years.

Juvenile Alexander disease is characterized by talking and swallowing difficulty and inability to cough. Age of onset is usually between 4 and 10 years of age. Affected children survive 10-30 years.

Adult-onset Alexander disease is relatively rare, and variable compared to the other two forms. The adult-onset form is generally similar to the juvenile form, though the symptoms are milder. Some patients may also manifest difficulties in talking, swallowing and walking, sleep disturbance, and ataxia.

Genetics

Alexander disease is inherited in an autosomal dominant manner, and GFAP is the only known causative gene for this disease (Messing et al. 2012). Most patients have a de novo pathogenic variant. Penetrance is very high (nearly 100%) in patients with the infantile and juvenile forms of Alexander disease (Li et al. 2002; Messing et al. 2003).

GFAP encodes glial fibrillary acidic protein, which is an intermediate filament protein mainly expressed in mature astrocytes of the central nervous system. GFAP is a cytoskeletal protein regulating the morphology and motility of astrocytes (Eng et al. 2000). To date, over 100 pathogenic variants have been identified in GFAP to cause Alexander disease. Of note, more than 90% of pathogenic variants (96/106) in GFAP are missense, suggesting a toxic gain of function mechanism (Human Gene Mutation Database); however, the exact mechanism underlying Alexander disease remains unclear. GFAP with pathogenic variants may impair the oligomerization or solubility of protein molecules synthesized from the normal allele (Hsiao et al. 2005; Der Perng et al. 2006).

Clinical Sensitivity - Sequencing with CNV PGxome

The clinical sensitivity of this test is expected to be high. Based on published reports, about 98% of patients with a diagnosis of Alexander disease have a pathogenic variant in GFAP (Srivastava et al. 2002).

Testing Strategy

This test provides full coverage of all coding exons of the GFAP gene 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 full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with clinical symptoms consistent with Alexander disease are candidates for this test.

Gene

Official Gene Symbol OMIM ID
GFAP 137780
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Alexander Disease AD 203450

Citations

  • Der Perng M. et al. 2006. American Journal of Human Genetics. 79: 197-213. PubMed ID: 16826512
  • Eng L.F. et al. 2000. Neurochemical Research. 25: 1439-51. PubMed ID: 11059815
  • Hsiao VC et al. 2005. Journal of Cell Science. 118: 2057-65. PubMed ID: 15840648
  • Human Gene Mutation Database (Bio-base).
  • Li R. et al. 2002. International Journal of Developmental Neuroscience. 20: 259-68. PubMed ID: 12175861
  • Messing A. et al. 2012. The Journal of Neuroscience. 32: 5017-23. PubMed ID: 22496548
  • Messing A., Brenner M. 2003. The Lancet. Neurology. 2: 75. PubMed ID: 12849260
  • Srivastava S. et al. Alexander Disease. 2002. In: Pagon RA, Adam MP, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews™, Seattle (WA): University of Washington, Seattle. PubMed ID: 20301351

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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ORDER OPTIONS

View Ordering Instructions

1) Select Test Method (Backbone)


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.

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