Mutant neutrophil elastase gene (ELANE) (ELANE)

The mutant ELANE allele DNA refers to the genomic sequence of the neutrophil elastase gene harboring pathogenic mutations, which are the primary cause of severe congenital neutropenia (SCN) and cyclic neutropenia. These mutations typically lead to the production of misfolded neutrophil elastase protein, which accumulates in the endoplasmic reticulum of myeloid progenitor cells, triggering the unfolded protein response (UPR) and subsequent apoptosis, a phenomenon termed 'marrow stoppage' (Horwitz et al., Blood, 2013). Targeting the mutant allele specifically at SNP-linked loci allows for precision gene-editing approaches, such as CRISPR/Cas9, to selectively disrupt the expression of the toxic mutant protein while preserving the functional wild-type allele (Nasri et al., Nature Communications, 2020). This allele-specific strategy is vital because while the mutant protein is cytotoxic, ELANE haploinsufficiency is generally well-tolerated, making gene knockout a viable therapeutic path. Current research focuses on utilizing patient-specific single nucleotide polymorphisms (SNPs) to guide nucleases to the mutant locus, aiming to restore effective granulopoiesis in affected individuals.

Other names

ELANEELA2Neutrophil elastase geneSCN1Mutant ELANE alleleNeutrophil elastase mutant DNA

Allele-specific gene knockout, Gene editing, Gene silencing