Novel genetic etiologies of severe congenital neutropenia.
Severe congenital neutropenia (SCN) comprises a heterogenous group of primary immunodeficiency disorders collectively characterized by paucity of mature neutrophils. In recent years, progress has been made with respect to the elucidation of genetic causes underlying syndromic and non-syndromic variants of SCN. Most cases of autosomal dominant SCN are associated with mutations in the neutrophil elastase (ELA-2/ELANE) gene, autosomal recessive forms of this disorder can be caused by mutations in the gene encoding the mitochondrial protein HAX-1. Rarely, SCN can be caused by mutations in the gene encoding the transcription factor GFI1 or activating mutations in the Wiskott-Aldrich syndrome (WAS) gene, respectively. More recently, a complex disorder associating SCN and developmental aberrations was identified, caused by mutations in the glucose-6-phosphatase catalytic subunit 3 (G6PC3) gene. Despite our increasing knowledge of the genetic etiologies of SCN, the molecular pathophysiology underlying these disorders remains only partially understood.
Boztug
Kaan
K
Department of Pediatric Hematology/Oncology, Hannover Medical School, Carl-Neuberg-Strasse 1, D-30625 Hannover, Germany.
Klein
Christoph
C
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005952:Glucose-6-Phosphatase / Q000235:genetics; D006801:Humans; D019272:Leukocyte Elastase / Q000235:genetics; D009154:Mutation; D009503:Neutropenia / Q000151:congenital / Q000235:genetics*; D011506:Proteins / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D051316:Wiskott-Aldrich Syndrome Protein / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C498275:GFI1 protein, human; C104759:HAX1 protein, human; D011506:Proteins; D014157:Transcription Factors; C495767:WAS protein, human; D051316:Wiskott-Aldrich Syndrome Protein; D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human; D019272:Leukocyte Elastase