Costello Syndrome via the HRAS 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 | |
|---|---|---|---|---|---|
| 9175 | HRAS | 81404 | 81404,81479 | $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
Costello syndrome (CS OMIM 218040) is a rare multiple congenital anomaly that overlaps phenotypically with Noonan syndrome (NS OMIM 163950) and cardio-facio-cutaneous syndrome (CFCS OMIM 115150). CS is characterized by coarse facial features with wide forehead, depressed nasal bridge and full cheeks; thick and loose skin of the hands and feet; papillomata; heart defects, mainly pulmonary valve stenosis, rhythm disturbances and hypertrophic cardiomyopathy; increased growth at the prenatal stage followed by postnatal growth retardation; short stature; relative macrocephaly and mild to moderate mental retardation (Van Eeghen et al. A J Med Genet 82:187-193, 1999; Lin et al. A J Med Genet 111:115-129, 2002). Patients with CS are at risk of developing benign and malignant tumors, most commonly rhabdomyosarcoma. Neuroblastoma and bladder carcinoma have also been reported (Gripp et al. Am J Med Genet A 140:1-7, 2006).
Genetics
CS syndrome is caused by variants in the HRAS gene (Aoki et al. Nat Genet 37:1038-1040, 2005). Twelve heterozygous germline variants have been reported in patients with CS. The majority of variants affect codons G12 and G13. However, variants affecting other codons have been reported. Most CS cases are sporadic resulting from de novo HRAS variants. Although rare, somatic and germline mosaicism has been reported (Girisha et al. Am J Med Genet A 152A:2861- 2864, 2010; Sol-Church et al. Am J Med Genet A 149A:315-321, 2009). The HRAS protein is a member of the RAS protein family, which is involved in cell signaling pathways, cell growth and apoptosis. Somatic HRAS variants, including variants that affect codons G12 and G13, have been implicated in several human cancers.
Clinical Sensitivity - Sequencing with CNV PG-Select
This test will detect causative HRAS variants in 80-90% of CS patients (Gripp and Lin, Genet Med 14:285-92, 2012).
Testing Strategy
This test provides full coverage of all coding exons of the HRAS gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.
Indications for Test
Candidates for this test are patients with symptoms consistent with a diagnosis of CS. As the clinical features of cardio-facio-cutaneous syndrome and Noonan syndrome overlap with CS, patients who test negative for the genes most commonly associated with those conditions are also candidates.
Candidates for this test are patients with symptoms consistent with a diagnosis of CS. As the clinical features of cardio-facio-cutaneous syndrome and Noonan syndrome overlap with CS, patients who test negative for the genes most commonly associated with those conditions are also candidates.
Gene
| Official Gene Symbol | OMIM ID |
|---|---|
| HRAS | 190020 |
| Inheritance | Abbreviation |
|---|---|
| Autosomal Dominant | AD |
| Autosomal Recessive | AR |
| X-Linked | XL |
| Mitochondrial | MT |
Disease
| Name | Inheritance | OMIM ID |
|---|---|---|
| Costello Syndrome | AD | 218040 |
Related Test
| Name |
|---|
| Comprehensive Cardiology Panel |
Citations
- Aoki Y, Niihori T, Kawame H, Kurosawa K, Ohashi H, Tanaka Y, Filocamo M, Kato K, Suzuki Y, Kure S, Matsubara Y. 2005. Germline mutations in HRAS proto-oncogene cause Costello syndrome. Nat. Genet. 37: 1038–1040. PubMed ID: 16170316
- Eeghen AM van, Gelderen I van, Hennekam RC. 1999. Costello syndrome: report and review. Am. J. Med. Genet. 82: 187–193. PubMed ID: 9934987
- Girisha et al. Am J Med Genet A 152A:2861-2864, 2010 PubMed ID: 20979192
- Gripp and Lin, (2012). Costello syndrome: a Ras/mitogen activated protein kinase pathway syndrome (rasopathy) resulting from HRAS germline mutations. Genet Med 14(3):285-92. PubMed ID: 22261753
- Gripp KW, Lin AE, Stabley DL, Nicholson L, Scott CI Jr, Doyle D, Aoki Y, Matsubara Y, Zackai EH, Lapunzina P, Gonzalez-Meneses A, Holbrook J, Agresta CA, Gonzalez IL, Sol-Church K. 2006. HRAS mutation analysis in Costello syndrome: genotype and phenotype correlation. Am. J. Med. Genet. A 140: 1–7. PubMed ID: 16329078
- Lin AE, Grossfeld PD, Hamilton RM, Smoot L, Gripp KW, Proud V, Weksberg R, Wheeler P, Picker J, Irons M, Zackai E, Marino B, Scott CI Jr, Nicholson L. 2002. Further delineation of cardiac abnormalities in Costello syndrome. Am. J. Med. Genet. 111: 115–129. PubMed ID: 12210337
- Sol-Church K, Stabley DL, Demmer LA, Agbulos A, Lin AE, Smoot L, Nicholson L, Gripp KW. 2009. Male-to-male transmission of Costello syndrome: G12S HRAS germline mutation inherited from a father with somatic mosaicism. American Journal of Medical Genetics Part A 149A: 315–321. PubMed ID: 19206176
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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