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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 GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
9175 HRAS 81404 81404,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
9175HRAS81404 81404(x1), 81479(x1) $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

  • Brett Deml, PhD

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.

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 Tests

Name
Comprehensive Cardiology Panel
Fetal Concerns 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


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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