title: Severe congenital neutropenia in a multigenerational family with a novel neutrophil elastase (ELANE) mutation.
abstract: We have analysed a family with nine congenital neutropenia patients in four generations, several of which we have studied in a long-term follow-up of over 25 years. The patients were mild to severe neutropenic and suffered from various recurrent bacterial infections. Mutations in the genes ELANE, CSF3R and GFI1 have been reported in patients with autosomal dominant congenital neutropenias. Using a small-scale linkage analysis with markers around the ELANE, CSF3R, CSF3 and GFI1 genes, we were able to determine that the disease segregated with markers around the ELANE gene. We identified a novel mutation in the ELANE gene in all of the affected family members that was not present in any of the healthy family members. The mutation leads to an A28S missense mutation in the mature protein. None of these patients developed leukaemia. This is the first truly multigenerational family with mutations in ELANE as unambiguous cause of severe congenital neutropenia SCN.
authors.affiliation: Department of Infectious Diseases, C5-P, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands. E.van_de_Vosse@LUMC.nl
authors.forename: Esther
authors.initials: E
authors.lastname: van de Vosse
authors.forename: Els M
authors.initials: EM
authors.lastname: Verhard
authors.forename: Anton J T
authors.initials: AJ
authors.lastname: Tool
authors.forename: Adriëtte W
authors.initials: AW
authors.lastname: de Visser
authors.forename: Taco W
authors.initials: TW
authors.lastname: Kuijpers
authors.forename: Pieter S
authors.initials: PS
authors.lastname: Hiemstra
authors.forename: Jaap T
authors.initials: JT
authors.lastname: van Dissel
mesh_terms: D023181:Antimicrobial Cationic Peptides / Q000097:blood; D002874:Chromosome Mapping; D000080984:Congenital Bone Marrow Failure Syndromes; D004252:DNA Mutational Analysis; D008040:Genetic Linkage; D005819:Genetic Markers; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics*; D009154:Mutation; D009503:Neutropenia / Q000097:blood / Q000151:congenital / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics; D009504:Neutrophils / Q000502:physiology; D010375:Pedigree; D000515:alpha 1-Antitrypsin / Q000378:metabolism; D054804:Cathelicidins
chemical_list: D023181:Antimicrobial Cationic Peptides; D005819:Genetic Markers; D000515:alpha 1-Antitrypsin; D016179:Granulocyte Colony-Stimulating Factor; D019272:Leukocyte Elastase; D054804:Cathelicidins
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