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 Genes | Test CPT Code | Gene CPT Codes Copy CPT Code | Base Price | |
|---|---|---|---|---|---|
| 3829 | SAMHD1 | 81479 | 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.
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.
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
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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