Ela2 mutations and clinical manifestations in familial congenital neutropenia

J Pediatr Hematol Oncol. 2009 May;31(5):319-24. doi: 10.1097/MPH.0b013e3181984dbe.


Purpose: Three familial cases of each of severe congenital neutropenia (SCN) and cyclic neutropenia (CN) in addition to 3 sporadic cases of SCN were analyzed for neutrophil elastase (Ela2) gene mutation. The contents of the neutrophil-specific granule proteins cathelicidin antimicrobial peptide and neutrophil gelatinase-associated lipocalin were also analyzed in SCN.

Methods: Genomic DNA was extracted from the patients' peripheral blood or bone marrow, and the coding sequence of the Ela2 gene was amplified by polymerase chain reaction and subjected to direct sequencing. The contents of antimicrobial peptides were analyzed by flow cytometry.

Results: Three cases of familial SCN (P13L, R52P, and S97L), 2 of familial CN (W212stop and P110L), and 1 of sporadic SCN (V72M) were shown to have heterozygous mutations in the Ela2 gene. W212stop found in a familial CN case was a novel mutation of Ela2. Prophylactic treatment for growth factors or antibiotic prophylaxis against bacterial infection was useful for lowering the frequency of infectious episodes. Adult patients tended to have less frequent infections compared with minors in the same family. The contents of both cathelicidin antimicrobial peptide and neutrophil gelatinase-associated lipocalin were significantly reduced in SCN compared with healthy controls.

Conclusions: Prophylaxis by growth factor or antibiotics is useful for decreasing risks of bacterial infections in SCN and CN. Adults were likely to have less frequent infections than children in familial cases of SCN and CN with the same mutation of Ela2.

MeSH terms

  • Adolescent
  • Adult
  • Antimicrobial Cationic Peptides / metabolism
  • Bacterial Infections / epidemiology
  • Bacterial Infections / genetics
  • Bacterial Infections / immunology
  • Child
  • Child, Preschool
  • Family Health
  • Female
  • Flow Cytometry
  • Genetic Predisposition to Disease / epidemiology
  • Humans
  • Leukocyte Elastase / genetics*
  • Male
  • Neutropenia / congenital*
  • Neutropenia / epidemiology
  • Neutropenia / genetics*
  • Neutrophils / cytology
  • Neutrophils / physiology*
  • Point Mutation*
  • Polymerase Chain Reaction
  • Risk Factors
  • Young Adult


  • Antimicrobial Cationic Peptides
  • ropocamptide
  • Leukocyte Elastase