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Noonan Syndrome via the SPRY1 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
12025 SPRY1 81479 81479,81479 $640 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
12025SPRY181479 81479(x2) $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

Noonan Syndrome (NS) is characterized by dysmorphic facial features, growth and congenital heart defects, and musculoskeletal abnormalities. Cardiac abnormalities are found in up to 80% of patients and include pulmonary valve stenosis, atrial septal defect, atrioventricular canal defect, and hypertrophic cardiomyopathy. Musculoskeletal abnormalities include short stature, chest deformity with sunken or raised sternum, and short webbed neck. Several additional abnormalities have been described and include renal, genital, hematological, neurologic, cognitive, behavioral, gastrointestinal, dental, and lymphatic findings. Intelligence is usually normal; however, learning disabilities may be present. NS is characterized by extensive clinical heterogeneity, even among members of the same family. Diagnosis is often made in infancy or early childhood. Symptoms often change and lessen with advancing age. Infants with NS are at risk of developing juvenile myelomonocytic leukemia (JMML). The prevalence of NS is estimated at 1 in 1,000 to 1 in 2,500 births worldwide (Allanson. 1987. PubMed ID: 3543368; Romano et al. 2010. PubMed ID: 20876176; Smpokou et al. 2012. PubMed ID: 23165751; Cao et al. 2017. PubMed ID: 28643916).

Clinical features of Noonan syndrome overlap with those of Cardio-Facio-Cutaneous syndrome (Gripp et al. 2007. PubMed ID: 17551924; Rauen. 2016. PubMed ID: 20301365), and Costello syndrome (Gripp and Lin. 2012. PubMed ID: 20301680).

Genetics

Noonan and Noonan-like syndromes are caused by pathogenic variants in PTPN11, SOS1, RAF1, KRAS, SHOC2, BRAF, NRAS, CBL, KAT6B, RIT1, SOS2, LZTR1, MAP3K8, SPRY1, NF1, RRAS, RASA2, and A2ML1 (Human Gene Mutation Database).

To date, three distinct pathogenic variants in the SPRY1 gene have been identified via whole exome sequencing. These cases include one individual with Noonan syndrome, one individual with cardiac and neurodevelopmental abnormalities, and three family members with craniosynostosis (Chen et al. 2014. PubMed ID: 25049390; Jin. 2017. PubMed ID: 28991257; Timberlake et al. 2016. PubMed ID: 27606499). Evidence for pathogenicity include: de novo origin of variants in three sporadic cases and co-segregation of one variant with craniosynostosis in a familial case; and functional studies in mice demonstrating that the conditional expression of SPRY1 in neural crest cells result in craniofacial and cardiac abnormalities, whilst SPRY1-null mice exhibit kidney and urinary tract abnormalities (Yang et al. 2010. PubMed ID: 20459789, Basson et al. 2005. PubMed ID: 15691764).

The SPRY1 gene encodes the sprouty homolog 1 protein, which acts as a negative regulator of Ras/MAPK/RTK signaling across a variety of systems in embryonic and adult tissues (Kim and Bar-Sagi. 2004. PubMed ID: 15173823). It is hypothesized that SPRY1 may regulate signaling pathways that have been implicated in Noonan spectrum disorders, however, the exact molecular mechanism underlying inhibition remain unclear (Tidyman and Rauen. 2016. PubMed ID: 27942422).

Clinical Sensitivity - Sequencing with CNV PG-Select

Pathogenic variants in the SPRY1 gene appear to be a rare cause of Noonan Syndrome. A whole exome sequencing study of 27 Noonan Syndrome cases lacking a causative variant in a known disease-associated gene identified a single individual carrying a de novo nonsense variant in SPRY1 (Chen et al. 2014. PubMed ID: 25049390).

Testing Strategy

This test provides full coverage of all coding exons of the SPRY1 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 clinical features within the Noonan spectrum disorders.

Gene

Official Gene Symbol OMIM ID
SPRY1 602465
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Disease

Name Inheritance OMIM ID

Citations

  • Allanson. 1987. PubMed ID: 3543368
  • Basson et al. 2005. PubMed ID: 15691764
  • Cao et al. 2017. PubMed ID: 28643916
  • Chen et al. 2014. PubMed ID: 25049390
  • Gripp and Lin. 2012. PubMed ID: 20301680
  • Gripp et al. 2007. PubMed ID: 17551924
  • Human Gene Mutation Database (Biobase).
  • Jin. 2017. PubMed ID: 28991257
  • Kim and Bar-Sagi. 2004. PubMed ID: 15173823
  • Rauen. 2016. PubMed ID: 20301365
  • Romano et al. 2010. PubMed ID: 20876176
  • Smpokou et al. 2012. PubMed ID: 23165751
  • Tidyman and Rauen. 2016. PubMed ID: 27942422
  • Timberlake et al. 2016. PubMed ID: 27606499
  • Yang et al. 2010. PubMed ID: 20459789

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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