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Aicardi-Goutières Syndrome 3 via the RNASEH2C 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
RNASEH2C 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
3827RNASEH2C81479 81479,81479 $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.

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 3 is inherited in an autosomal recessive manner due to pathogenic variants in RNASEH2C, located on chromosome 11q13.1. RNASEH2C encodes the subunit C of the human ribonuclease H2 enzyme complex which cleaves ribonucleotides from RNA:DNA duplexes. Missense pathogenic variants are most commonly reported; however, some small deletion/insertion variants have been reported as well (Human Gene Mutation Database). The RNASEH2C variant c.205C>T (p.Arg69Trp) is seen particularly frequently in Asian (most commonly Pakistani) families and represents an ancient founder event (Rice et al 2007).

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, no large deletions or duplications involving the RNASEH2C gene have been reported.

Testing Strategy

This test provides full coverage of all coding exons of the RNASEH2C 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 RNASEH2C.

Gene

Official Gene Symbol OMIM ID
RNASEH2C 610330
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID
Aicardi-Goutieres Syndrome 3 AR 610329

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
  • Human Gene Mutation Database (Bio-base).
  • Rice G. et al. 2007. American Journal of Human Genetics. 81: 713-25. PubMed ID: 17846997
  • 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

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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2) Select Additional Test Options

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