Severe Congenital Neutropenia (Dursun Syndrome) via the G6PC3 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
8795 G6PC3 81479 81479,81479 $890 Order Options and Pricing
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8795G6PC381479 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.

For Reflex to PGxome pricing click here.

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 14 days on average for STAT orders.

Once a specimen has started the testing process in our lab, the most accurate prediction of TAT will be displayed in the myPrevent portal as an Estimated Report Date (ERD) range. We calculate the ERD for each specimen as testing progresses; therefore the ERD range may differ from our published average TAT. View 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

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 (ANCs) consistently below 500/ul and severe systemic bacterial infections beginning in early infancy (Boxer and Newburger 2007). Patients typically have recurrent fevers and develop sinusitis, gingivitis and other soft tissue infections. A prominent feature of SCN is bone marrow ‘maturation arrest’; neutrophils differentiate only to the promyelocyte/myelocyte stage (Kostman 1975). Mature neutrophils are few in number and are deficient in their antibacterial abilities. About 95% of patients respond to treatment with recombinant granulocyte-colony stimulating factor (G-CSF) with an increase in ANC (Bellanne-Chantelot et al. 2004; Freedman et al. 2000). G-CSF reverses neutropenia and decreases infections, but treated patients are still at risk of sepsis (Donini et al. 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 malignancy increases upon G-CSF treatment (Gilman et al. 1970; Freedman et al. 2000; Rosenberg et al. 2006). In contrast to SCN, MDS/AML have not been diagnosed in patients with cyclic or idiopathic neutropenia.

Genetics

Autosomal recessive forms of SCN have been linked to mutations in the G6PC3 and HAX1 genes. Mutations in the G6PC3 (OMIM 611045) gene result in a very severe form of SCN in which neutropenia is accompanied by developmental defects including structural heart defects, urogenital abnormalities, and venous angiectasia of the trunk and extremities (Boztug et al. 2009). The G6PC3 phenotype has been extended to include monocytosis, lymphopenia, and erythroid hypoplasia resulting in anemia (Dursun et al. 2009). In addition to the above conditions, mutations in G6PC3 have also been connected to inflammatory bowel disease (Begin et al. 2013). Causative mutations are primarily missense and nonsense, but splice site mutations and small insertions and deletions have been reported (Aróstegui et al. 2009; Xia et al. 2009). G6PC3 encodes glucose-6-phosphatase (G6P), catalytic subunit 3. G6P is an Endoplasmic Reticulum protein that catalyzes hydrolysis of glucose-6-phosphate to glucose and phosphate. Defective G6P is thought to cause Endoplasmic Reticulum stress in neutrophil precursors resulting in apoptosis and reduced ANCs (Boztug et al. 2009).

Clinical Sensitivity - Sequencing with CNV PGxome

Mutations in G6PC3 cause a rare form of neutropenia that represents a small fraction of all SCN cases.

No gross deletions/duplications large enough to be detected by PreventionGenetics' aCGH have been reported in G6PC3 (Human Gene Mutation Database).

Testing Strategy

This test provides full coverage of all coding exons of the G6PC3 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.

Since this test is performed using exome capture probes, a reflex to any of our exome based tests is available (PGxome, PGxome Custom Panels).

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). This test may also be considered for the reproductive partners of individuals who carry pathogenic variants in G6PC3.

Gene

Official Gene Symbol OMIM ID
G6PC3 611045
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Citations

  • Arostegui JI, Toledo JS de, Pascal M, Garcia C, Yague J, Diaz de Heredia C. 2009. A novel G6PC3 homozygous 1-bp deletion as a cause of severe congenital neutropenia. Blood 114: 1718–1719. PubMed ID: 19696212
  • Bégin P1, Patey N, Mueller P, Rasquin A, Sirard A, Klein C, Haddad E, Drouin É, Le Deist F. 2013. Inflammatory bowel disease and T cell lymphopenia in G6PC3 deficiency. Journal of Clinical Immunology 33(3):520-5. PubMed ID: 23180359
  • 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
  • Boztug K, Appaswamy G, Ashikov A, Schäffer AA, Salzer U, Diestelhorst J, Germeshausen M, Brandes G, Lee-Gossler J, Noyan F. 2009. A syndrome with congenital neutropenia and mutations in G6PC3. New England Journal of Medicine 360: 32–43. PubMed ID: 19118303
  • 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
  • Dursun A, Ozgul RK, Soydas A, Tugrul T, Gurgey A, Celiker A, Barst RJ, Knowles JA, Mahesh M, Morse JH. 2009. Familial pulmonary arterial hypertension, leucopenia, and atrial septal defect: a probable new familial syndrome with multisystem involvement: Clinical Dysmorphology 18: 19–23. PubMed ID: 19011569
  • 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
  • Human Gene Mutation Database (Bio-base).
  • 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
  • Xia J, Bolyard AA, Rodger E, Stein S, Aprikyan AA, Dale DC, Link DC. 2009. Prevalence of mutations in ELANE , GFI1 , HAX1 , SBDS , WAS and G6PC3 in patients with severe congenital neutropenia. British Journal of Haematology 147: 535–542. PubMed ID: 19775295

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.

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

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