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Aicardi-Goutières Syndrome 5 via the SAMHD1 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
3829 SAMHD1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3829SAMHD181479 81479,81479 $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

  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Aicardi-Goutiéres syndrome (AGS) is a rare, early-onset, progressive encephalopathy typically characterized by basal ganglia calcification, white matter abnormalities, and cerebral atrophy (Crow and Livingston 2008; Crow and Manel 2015). Affected individuals can present with progressive microcephaly, hypotonia, dystonia, seizures, spastic quadriplegia, and severe developmental delay (Crow 2014). Chilblains, glaucoma, hypothyroidism, cardiomyopathy, intracerebral vasculitis, peripheral neuropathy, and systemic lupus erythematosus are also associated with the AGS spectrum of disease (Crow et al. 2015). Cerebrospinal fluid analyses show lymphocytosis and increased type I interferon activity. AGS individuals are often misdiagnosed with congenital infections due to similar presentation. Onset can occur in utero (~25%), while the majority of patients present within the first year of life (~70%) (Crow et al. 2015). Recently, six interferon-stimulated genes were measured and found to be useful biomarkers in most AGS patients (Rice et al. 2013).

Genetics

Aicardi-Goutières Syndrome 5 is inherited in an autosomal recessive manner due to pathogenic variants in SAMHD1, located on chromosome 20pter-q12. SAMHD1 encodes the sterile alpha motif domain and HD domain containing protein 1 (SAMHD1) which is a nucleic-acid-binding protein. Most pathogenic variants have been found to result in altered protein subcellular localization that results in cytosolic accumulation of the SAMHD1 protein (Goncalves et al. 2012). Missense, nonsense, splicing, and small deletions/duplications, and about 10 gross deletions have all been reported in the SAMHD1 gene (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PG-Select

In a recent comprehensive study of 374 patients (299 families) with a molecular diagnosis of AGS, pathogenic variants were found in the following percentages: 23% TREX1, 5% RNASEH2A, 36% RNASEH2B, 12% RNASEH2C, 13% SAMHD1, 7% ADAR, and 3% IFIH1 (Crow et al. 2015).

Thus far, about 10 large deletions involving the SAMHD1 gene have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the SAMHD1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

Indications for Test

Patients with clinical features consistent with AGS, chronic leukocytosis, and increased interferon-alpha (INF-a) and neopterin in cerebrospinal fluid. This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in SAMHD1.

Gene

Official Gene Symbol OMIM ID
SAMHD1 606754
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Aicardi-Goutieres Syndrome 5 AR 612952

Related Test

Name
Aicardi-Goutières Syndrome Panel

Citations

  • Crow Y.J. 2014. Aicardi-Goutières Syndrome. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJ, Bird TD, Dolan CR, Fong C-T, Smith RJ, and Stephens K, editors. GeneReviews(®), Seattle (WA): University of Washington, Seattle. PubMed ID: 20301648
  • Crow Y.J. et al. 2015. American Journal of Medical Genetics. Part A. 167A: 296-312. PubMed ID: 25604658
  • Crow Y.J., Livingston J.H. 2008. Developmental Medicine and Child Neurology. 50: 410-6. PubMed ID: 18422679
  • Crow Y.J., Manel N. 2015. Nature Reviews. Immunology. 15: 429-40. PubMed ID: 26052098
  • Goncalves A. et al. 2012. Human Mutation. 33: 1116-22. PubMed ID: 22461318
  • Human Gene Mutation Database (Bio-base).
  • Rice G.I. et al. 2013. The Lancet. Neurology. 12: 1159-69. PubMed ID: 24183309

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

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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