DNA icon

Severe Congenital Neutropenia and Cyclic Neutropenia via the ELANE Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
8943 ELANE 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8943ELANE81479 81479,81479 $890 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information. If the Sanger option is selected, CNV detection may be ordered through Test #600.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing backbone).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing backbone).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

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

  • Siwu Peng, PhD

Clinical Features and Genetics

Clinical Features

Severe congenital neutropenia (SCN) comprises a heterogeneous group of disorders of myelopoiesis with varying symptoms and patterns of inheritance. SCN is characterized by absolute neutrophil counts (ANC) consistently below 500/µl and severe systemic bacterial infections beginning in early infancy (Boxer and Newburger. Pediatr Blood Cancer 49:609-614, 2007). Patients typically have recurrent fevers and develop sinusitis, gingivitis, and other soft tissue infections. SCN and cyclic neutropenia share the same symptoms; however, with cyclic neutropenia ANCs rise and fall with a periodicity of ~ 21-days. A hallmark of SCN is bone marrow "maturation arrest;" neutrophils differentiate only to the promyelocyte/myelocyte stage (Kostman. Acta Paediatr Scand 64:362-368, 1975). About 95% of patients respond to treatment with recombinant granulocyte-colony stimulating factor (G-CSF) with an increase in ANC (Bellanne-Chantelot et al. Blood 103:4119-4125, 2004; Freedman et al. Blood 96:429-436, 2000); however, treated patients are still at risk of sepsis (Donini et al. Blood 109:4716-4723, 2007). SCN is a premalignant condition; patients are at an elevated risk of developing myelodysplastic syndrome and acute myeloblastic leukemia (MDS/AML). The risk of developing a malignancy increases upon G-CSF treatment (Gilman et al. Blood 36:576-585, 1970; Freedman et al. Blood 96:429-436, 2000; Rosenberg et al. Blood 107:4628-4635, 2006). In contrast to patients with SCN, MDS/AML have not been diagnosed in patients with cyclic or idiopathic neutropenia.

Genetics

It is estimated that approximately 35%-63% of patients with neutropenia have heterozygous variants in the ELANE gene (OMIM 130130) (Rosenberg et al. Blood 107:4628-4635, 2006; Bellanne-Chantelot et al Blood 103:4119-4125, 2004). Causative variants are primarily missense and nonsense variants. ELANE encodes neutrophil elastase, a serine protease that cleaves cellular and extracellular proteins and is expressed exclusively in neutrophils and monocytes. Recent reports suggest that mutated elastase in the ER triggers the unfolded protein response in neutrophils causing apoptosis and neutropenia (Ward and Dale Curr Opin Hematol 16:9-13, 2009). In comparison to other neutropenia-related genes, variants in ELANE correlate with a more severe expression of the disease, particularly in cases of congenital neutropenia (Bellanne-Chantelot et al. Blood 103:4119-4125, 2004).

Clinical Sensitivity - Sequencing with CNV PGxome

ELANE variants are the most common cause of SCN and the only known cause of cyclic neutropenia.

Testing Strategy

This test provides full coverage of all coding exons of the ELANE gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with recurring bacterial infections, a family history of SCN, or neutropenia unrelated to other syndromes (e.g. Chediak-Higashi syndrome, Hermansky Pudlak syndrome, or Griscelli syndrome).

Gene

Official Gene Symbol OMIM ID
ELANE 130130
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Name
Severe Congenital Neutropenia and Neutrophilia via the CSF3R Gene

Citations

  • Bellanne-Chantelot C. 2004. Mutations in the ELA2 gene correlate with more severe expression of neutropenia: a study of 81 patients from the French Neutropenia Register. Blood 103: 4119–4125. PubMed ID: 14962902
  • Boxer LA, Newburger PE. 2007. A molecular classification of congenital neutropenia syndromes. Pediatric Blood & Cancer 49: 609–614. PubMed ID: 17584878
  • Donini M, Fontana S, Savoldi G, Vermi W, Tassone L, Gentili F, Zenaro E, Ferrari D, Notarangelo LD, Porta F, Facchetti F, Notarangelo LD, et al. 2007. G-CSF treatment of severe congenital neutropenia reverses neutropenia but does not correct the underlying functional deficiency of the neutrophil in defending against microorganisms. Blood 109: 4716–4723. PubMed ID: 17311988
  • Freedman MH, Bonilla MA, Fier C, Bolyard AA, Scarlata D, Boxer LA, Brown S, Cham B, Kannourakis G, Kinsey SE. 2000. Myelodysplasia syndrome and acute myeloid leukemia in patients with congenital neutropenia receiving G-CSF therapy. Blood 96: 429–436. PubMed ID: 10887102
  • Gilman PA, Jackson DP, Guild HG. 1970. Congenital agranulocytosis: prolonged survival and terminal acute leukemia. Blood 36: 576–585. PubMed ID: 4319697
  • Kostman R. 1975. Infantile genetic agranulocytosis. A review with presentation of ten new cases. Acta Paediatr Scand 64: 362–368. PubMed ID: 1130195
  • Rosenberg PS. 2006. The incidence of leukemia and mortality from sepsis in patients with severe congenital neutropenia receiving long-term G-CSF therapy. Blood 107: 4628–4635. PubMed ID: 16497969
  • Ward, A. C., Dale, D. C. (2009). "Genetic and molecular diagnosis of severe congenital neutropenia." Curr Opin Hematol 16(1): 9-13. PubMed ID: 19057199

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

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

loading Loading... ×

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: $
×
Copy Text to Clipboard
×