Phagocyte Defects

Gene: ELANE

Green List (high evidence)

The disease mechanism is unclear; however, considering current evidence it is unlikely that haploinsufficiency is a disease mechanism, and it is likely that the cause of neutropenia is not the lack of neutrophil elastase itself, but protease malfunction (PMID: 33968054)

According to ClinGen, there is little evidence for haploinsufficiency. gnomAD pLI score is zero and there are NMD predicted variants in the population.

Entire gene deletion is not described in the context of neutropenia, including deletion of 19p terminal (encompassing ELANE) (PMID: 33968054).

Maturation arrest, the failure of the marrow myeloid progenitors to form mature neutrophils, is a consistent feature of ELANE associated congenital neutropenia. Knock-out of the mutant allele in hematopoietic stem cells derived from SCN patients restores neutrophils maturation (PMID: 3124897).

Created: 31 Oct 2023, 1:42 a.m. | Last Modified: 31 Oct 2023, 1:42 a.m.

Panel Version: 1.19

Well established gene-disease association.

Severe congenital neutropaenia is a heterogeneous disorder of haematopoiesis characterized by a maturation arrest of granulopoiesis at the level of promyelocytes with peripheral blood absolute neutrophil counts below 0.5 x 10(9)/l and early onset of severe bacterial infections. About 60% of affected individuals of European and Middle Eastern ancestry have dominant ELANE mutations.

Created: 25 Jul 2021, 8:11 a.m. | Last Modified: 25 Jul 2021, 8:13 a.m.

Panel Version: 0.87

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Neutropaenia, severe congenital 1, autosomal dominant, MIM# 202700; Neutropaenia, cyclic, MIM# 162800

Publications

• 10581030
• 11001877
• 33968054
• 3124897

Mode of pathogenicity
Loss-of-function variants (as defined in pop up message) DO NOT cause this phenotype - please provide details in the comments