Recently, the identification of several novel genetic defects (e.g., p14-deficiency, HAX1-deficiency, AK2-deficiency) has shed light on the pathophysiology of congenital neutropenia.
Severe congenital neutropenia (SCN) is a genetically heterogeneous syndrome associated with mutations of ELANE (ELA2), HAX1, GFI1, WAS, CSF3R or G6PC3.
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.
Central nervous system involvement in severe congenital neutropenia: neurological and neuropsychological abnormalities associated with specific HAX1 mutations.
After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann.
After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann.
After further molecular screening of individuals with SCN, we identified 19 additional affected individuals with homozygous HAX1 mutations, including three belonging to the original pedigree described by Kostmann.
The recent findings include identification of mutations in HAX1 in autosomal recessive severe congenital neutropenia (Kostmann disease), a large epidemiological study estimating the risk of progression from severe congenital neutropenia to leukemia, a better understanding of how heterozygous mutations in neutrophil elastase (ELA2) cause severe congenital neutropenia, molecular characterization of a novel syndromic form of severe congenital neutropenia called p14 deficiency and new animal models for several syndromic forms of severe congenital neutropenia.