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severe congenital neutropenias

Tuesday 13 April 2004

Mutations in the HAX1 gene are associated with most cases of recessive autosomal severe congenital neutropenia, while ELA2 mutations are found in most cases of autosomal dominant and sporadic cases.

The role of HAX-1 protein as a regulatory step in apoptosis provides further evidence for severe congenital neutropenia as a disorder of programmed cell death.

The preleukemic character of severe congenital neutropenia, particularly for patients with need for high granulocyte colony stimulating factor dosage, was recently emphasized.


- autosomal dominant congenital agranulocytosis

  • autosomal dominant or sporadic congenital neutropenia (SCN1 at 19p13.3) (MIM.202700) is caused by germline mutation in the neutrophil elastase gene (ELA2) MIM.130130)

- autosomal recessive congenital agranulocytosis
- sporadic agranulocytosis

Mutations in the protooncogene GFI1 (MIM.600871), which targets ELA2, also cause neutropenia (SCN2). As in the case of the ELA2 mutations, those in GFI1 causing neutropenia are heterozygous.


- SCN1: germline mutations in the gene ELA2 encoding neutrophil elastase (NE) in autosomal recessive congenital agranulocytosis (Kostmann disease)

  • (also cause the human diseases cyclic neutropenia)

- SCN2: germline mutations in the protooncogene GFI1 (MIM.600871)

  • GFI1 product targets ELA2

- SCN3: Autosomal recessive severe congenital neutropenia (Kostmann disease) (MIM.610738)

  • SCN3 is caused by homozygous mutations in the HAX1 gene (MIM.605998).

See also

- Kostmann disease (autosomal recessive congenital agranulocytosis)


- Chronic idiopathic neutropenias and severe congenital neutropenia. Palmblad J, Papadaki HA. Curr Opin Hematol. 2008 Jan;15(1):8-14. PMID: 18043240

- Horwitz M, Benson KF, Duan Z, Li FQ, Person RE. Hereditary neutropenia: dogs explain human neutrophil elastase mutations. Trends Mol Med. 2004 Apr;10(4):163-70. PMID: 15059607