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Severe Congenital Neutropenia (Kostmann Disease) via the HAX1 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
HAX1 81479 81479,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
7691HAX181479 81479,81479 $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.


Genetic Counselors


  • 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.


Autosomal recessive forms of SCN have been linked to variants in the G6PC3 and HAX1 genes. Patients with Kostmann disease (Kostmann R. Acta Paediatr 45:1-78, 1956), autosomal recessive SCN due to variants in the HAX1 gene (OMIM 605998), may have neurological symptoms including cognitive dysfunction and epilepsy (Klein et al. Nat Genet 39:86-92, 2007; Germeshausen et al. Blood 111:4954-4957, 2008). HAX1 encodes a ubiquitously expressed mitochondrial protein that has an anti-apoptotic function (Cilenti et al. J Biol Chem 279:50295-50301, 2004). Klein et al. (2007) showed that HAX1 protects myeloid cells from apoptosis through its role in maintaining mitochondrial membrane potential. Consequently, disruption of normal HAX1 function affects neutrophil development resulting in SCN.

Clinical Sensitivity - Sequencing with CNV PG-Select

Autosomal recessive forms of SCN account for ~ 40% of SCN cases.

Testing Strategy

This test provides full coverage of all coding exons of the HAX1 gene, plus ~10 bases of flanking noncoding DNA. We define full coverage as >20X NGS reads or Sanger sequencing.

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 HAX1.


Official Gene Symbol OMIM ID
HAX1 605998
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT


Name Inheritance OMIM ID
Severe Congenital Neutropenia Autosomal Recessive 3 AR 610738

Related Tests

Severe Congenital Neutropenia and Neutrophilia via the CSF3R Gene
Severe Congenital Neutropenia Panel


  • 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
  • Cilenti, L., et.al. (2004). "Regulation of HAX-1 anti-apoptotic protein by Omi/HtrA2 protease during cell death." J Biol Chem 279(48): 50295-301. PubMed ID: 15371414
  • 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
  • Germeshausen, M., et.al. (2008). "Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations." Blood 111(10): 4954-7. PubMed ID: 18337561
  • Gilman PA, Jackson DP, Guild HG. 1970. Congenital agranulocytosis: prolonged survival and terminal acute leukemia. Blood 36: 576–585. PubMed ID: 4319697
  • Klein, C., et.al. (2007). "HAX1 deficiency causes autosomal recessive severe congenital neutropenia (Kostmann disease)." Nat Genet 39(1): 86-92. PubMed ID: 17187068
  • Kostmann, R. (1956). "Infantile genetic agranulocytosis; agranulocytosis infantilis hereditaria." Acta Paediatr Suppl 45(Suppl 105): 1-78. PubMed ID: 13326376
  • 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


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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Note: acceptable specimen types are whole blood and DNA from whole blood only.
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