title: Kostmann's Disease and HCLS1-Associated Protein X-1 (HAX1).
abstract: Severe congenital neutropenia (SCN), originally described by the Swedish pediatrician Rolf Kostmann, constitutes a heterogeneous disorder associated with a dramatic decrease of peripheral neutrophil granulocytes. Patients suffer from life-threatening bacterial infections unless treated by recombinant human granulocyte colony stimulating factor (G-CSF) or allogeneic hematopoietic stem cells. This review is focused on the SCN variant caused by mutations in HCLS1 Associated Protein X-1 (HAX1) (SCN3, "Kostmann Disease"). HAX1 is a ubiquitously expressed protein with pleotropic functions, including control of cellular viability, migration, and cancer progression. Even though scientific evidence on the molecular mechanisms regarding HAX1 accumulates, no unified picture has emerged. This review highlights historical milestones and our current understanding of SCN related to mutations in HAX1.
authors.affiliation: Department of Pediatrics, Dr. von Hauner Children's Hospital, Ludwig-Maximilians-Universität München, Lindwurmstrasse 4, 80337, Munich, Germany. christoph.klein@med.uni-muenchen.de.
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D003131:Combined Modality Therapy; D000080984:Congenital Bone Marrow Failure Syndromes; D019468:Disease Management; D056726:Genetic Association Studies; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D049673:History, 20th Century; D006801:Humans; D007109:Immunity / Q000235:genetics; D009154:Mutation; D009503:Neutropenia / Q000151:congenital* / Q000175:diagnosis / Q000209:etiology / Q000266:history / Q000628:therapy; D010641:Phenotype; D021381:Protein Transport
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C104759:HAX1 protein, human
keywords: HAX1; Kostmann’s disease; Severe congenital neutropenia (SCN)