Heterozygous mutations of the gene encoding neutrophil elastase (ELA2) have been 
associated with cyclic neutropenia (CN) and severe congenital neutropenia (SCN). 
To date, 30 different mutations have been reported, but no correlation has been 
found with the degree of neutropenia. To address this issue, we analyzed the 
clinical, hematologic, and molecular characteristics of 81 unrelated patients 
with SCN (n = 54) or CN (n = 27). We identified mutations in 31 patients, two 
thirds of whom had sporadic forms. Familial cases were consistent with dominant 
inheritance. Seventeen novel mutations were identified, showing that the 
mutational spectrum encompasses not only the region encoding the mature enzyme 
but also the prodomains and promoter region. Genotype-phenotype analysis 
strongly suggested that ELA2 mutations correlate with more severe expression of 
neutropenia, specifically in patients diagnosed with SCN. This study underlines 
the importance of ELA2 molecular screening to identify patients who may be at 
particular risk of severe bacterial infections and/or acute myeloid 
leukemia/myelodysplasia. By phenotypic analysis of affected relatives and 
carriers of the same ELA2 mutations, we showed that the expression of 
neutropenia in CN and SCN may be either homogeneous or variable according to the 
type of mutations, suggesting different pathogenetic mechanisms.