Gene correction of HAX1 reversed Kostmann disease phenotype in patient-specific induced pluripotent stem cells.

ABSTRACT: Severe congenital neutropenia (SCN, Kostmann disease) is a heritable disorder characterized by a granulocytic maturation arrest. Biallelic mutations in HCLS1 associated protein X-1 (HAX1) are frequently detected in affected individuals, including those of the original pedigree described by Kostmann in 1956. To date, no faithful animal model has been established to study SCN mediated by HAX1 deficiency. Here we demonstrate defective neutrophilic differentiation and compensatory monocyte overproduction from patient-derived induced pluripotent stem cells (iPSCs) carrying the homozygous HAX1^W44X nonsense mutation. Targeted correction of the HAX1 mutation using the CRISPR-Cas9 system and homologous recombination rescued neutrophil differentiation an

SUBMITTER: Pittermann E 

PROVIDER: S-EPMC5737589 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature