Aicardi-Goutières Syndrome Panel

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy Genes Gene CPT Codes Copy CPT Codes
10237 ADAR 81479,81479 Order Options and Pricing
IFIH1 81479,81479
RNASEH2A 81479,81479
RNASEH2B 81479,81479
RNASEH2C 81479,81479
SAMHD1 81479,81479
TREX1 81479,81479
Test Code Test Copy Genes Panel CPT Code Gene CPT Codes Copy CPT Code Base Price
10237Genes x (7)81479 81479(x14) $890 Order Options and Pricing

Pricing Comments

We are happy to accommodate requests for testing single genes in this panel or a subset of these genes. The price will remain the list price. If desired, free reflex testing to remaining genes on panel is available. Alternatively, a single gene or subset of genes can also be ordered via our Custom Panel tool.

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).

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

AGS is an inflammatory disease that occurs due to pathogenic variants in the ADAR, IFIH1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and TREX1 genes (Crow et al. 2015). Each of these seven genes encode proteins that are involved in nucleotide metabolism/signaling. The innate immune response is likely triggered by endogenously-derived nucleic acids that are not processed correctly and are immunostimulatory (Rice et al. 2013; Crow and Manel 2015). TREX1 encodes a DNA 3' repair exonuclease I. RNASEH2A, RNASEH2B, and RNASEH2C encode three components of the RNase H2 endonuclease complex. SAMHD1 encodes a SAM and HD domain containing protein that functions as a deoxynucleoside triphosphate triphosphohydrolase. ADAR1 encodes an enzyme that catalyzes the hydrolytic deamination of adenosine to inosine in double-stranded RNA. IFIH1 encodes an RNA receptor that activates type I interferon signaling (Crow and Manel 2015).

The majority of AGS cases are inherited in an autosomal recessive manner. Pathogenic variants in the RNASEH2A, RNASEH2B, RNASEH2C, and SAMHD1 are inherited in an autosomal recessive manner, while variants in the ADAR and TREX1 genes can exhibit both autosomal recessive and dominant inheritance (Crow et al. 2015). Dominant disease causing variants in TREX1 include Asp18Asn and Asp200Asn and in ADAR, Gly1007Arg (Crow et al. 2015). IFIH1 pathogenic variants are inherited in an autosomal dominant manner and many times occur de novo (Rice et al. 2014; Oda et al. 2014).

ADAR pathogenic variants for AGS include missense and small deletions. ADAR variants can also be causative for dyschromatosis symmetrica hereditaria and include missense, nonsense, splicing, and small deletions and insertions. Missense, nonsense, splicing, and small insertions or deletions are found in the other genes in this panel (Human Gene Mutation Database). The RNASEH2B and SAMHD1 genes also have a small number of reported gross deletions that are not detectable by sequencing.

Clinical Sensitivity - Sequencing with CNV PGxome

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). Clinical sensitivity was found to be around 90% before the identification of the additional causative gene IFIH1 (Crow 2014). Therefore, clinical sensitivity for patients with clinical and radiologic findings consistent with AGS will be greater than 90%. Analytical sensitivity should be high, since only a few large deletions/duplications in the relevant genes have been reported.

Testing Strategy

This panel provides 100% coverage of all coding exons of the genes 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 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 features consistent with AGS, chronic leukocytosis, and increased interferon-alpha (INF-a) and neopterin in Cerebrospinal fluid.

Genes

Official Gene Symbol OMIM ID
ADAR 146920
IFIH1 606951
RNASEH2A 606034
RNASEH2B 610326
RNASEH2C 610330
SAMHD1 606754
TREX1 606609
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
PGxome®

Citations

  • Crow YJ, Chase DS, Lowenstein Schmidt J, Szynkiewicz M, Forte GMA, Gornall HL, Oojageer A, Anderson B, Pizzino A, Helman G, Abdel-Hamid MS, Abdel-Salam GM, Ackroyd S, Aeby A, Agosta G, Albin C, Allon-Shalev S, Arellano M, Ariaudo G, Aswani V, Babul-Hirji R, Baildam EM, Bahi-Buisson N, Bailey KM, Barnerias C, Barth M, Battini R, Beresford MW, Bernard G, Bianchi M, Billette de Villemeur T, Blair EM, Bloom M, Burlina AB, Carpanelli ML, Carvalho DR, Castro-Gago M, Cavallini A, Cereda C, Chandler KE, Chitayat DA, Collins AE, Sierra Corcoles C, Cordeiro NJ, Crichiutti G, Dabydeen L, Dale RC, D PubMed ID: 25604658
  • Crow YJ, Livingston JH. 2008. Aicardi-Goutières syndrome: an important Mendelian mimic of congenital infection. Developmental Medicine & Child Neurology 50: 410–416. PubMed ID: 18422679
  • Crow YJ, Manel N. 2015. Aicardi-Goutieres syndrome and the type I interferonopathies. Nat Rev Immunol advance online publication. PubMed ID: 26052098
  • Crow YJ. 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
  • Human Gene Mutation Database (Bio-base).
  • Oda H, Nakagawa K, Abe J, Awaya T, Funabiki M, Hijikata A, Nishikomori R, Funatsuka M, Ohshima Y, Sugawara Y, Yasumi T, Kato H, Shirai T, Ohara O, Fujita T, Heike T. 2014. Aicardi-Goutières Syndrome Is Caused by IFIH1 Mutations. The American Journal of Human Genetics 95: 121–125. PubMed ID: 24995871
  • Rice GI, Forte GMA, Szynkiewicz M, Chase DS, Aeby A, Abdel-Hamid MS, Ackroyd S, Allcock R, Bailey KM, Balottin U, Barnerias C, Bernard G, Bodemer C, Botella MP, Cereda C, Chandler KE, Dabydeen L, Dale RC, De Laet C, De Goede CG, Del Toro M, Effat L, Enamorado NN, Fazzi E, Gener B, Haldre M, Lin JP, Livingston JH, Lourenco CM, Marques W Jr, Oades P, Peterson P, Rasmussen M, Roubertie A, Schmidt JL, Shalev SA, Simon R, Spiegel R, Swoboda KJ, Temtamy SA, Vassallo G, Vilain CN, Vogt J, Wermenbol V, Whitehouse WP, Soler D, Olivieri I, Orcesi S, Aglan MS, Zaki MS, Abdel-Salam GM, Vanderver A, Kisand K, Rozenberg F, Lebon P, Crow YJ. 2013. Assessment of interferon-related biomarkers in Aicardi-Goutières syndrome associated with mutations in TREX1, RNASEH2A, RNASEH2B, RNASEH2C, SAMHD1, and ADAR: a case-control study. Lancet Neurol 12: 1159–1169. PubMed ID: 24183309
  • Rice GI, Toro Duany Y del, Jenkinson EM, Forte GMA, Anderson BH, Ariaudo G, Bader-Meunier B, Baildam EM, Battini R, Beresford MW, Casarano M, Chouchane M, Cimaz R, Collins AE, Cordeiro NJ, Dale RC, Davidson JE, De Waele L, Desguerre I, Faivre L, Fazzi E, Isidor B, Lagae L, Latchman AR, Lebon P, Li C, Livingston JH, Lourenço CM, Mancardi MM, Masurel-Paulet A, McInnes IB, Menezes MP, Mignot C, O PubMed ID: 24686847

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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