title: Digenic mutations in severe congenital neutropenia.
abstract: Severe congenital neutropenia a clinically and genetically heterogeneous disorder. Mutations in different genes have been described as causative for severe neutropenia, e.g. ELANE, HAX1 and G6PC3. Although congenital neutropenia is considered to be a group of monogenic disorders, the phenotypic heterogeneity even within the yet defined genetic subtypes points to additional genetic and/or epigenetic influences on the disease phenotype. We describe congenital neutropenia patients with mutations in two candidate genes each, including 6 novel mutations. Two of them had a heterozygous ELANE mutation combined with a homozygous mutation in G6PC3 or HAX1, respectively. The other 2 patients combined homozygous or compound heterozygous mutations in G6PC3 or HAX1 with a heterozygous mutation in the respective other gene. Our results suggest that digenicity may underlie this disorder of myelopoiesis at least in some congenital neutropenia patients.
authors.affiliation: Department of Pediatric Hematology and Oncology/Molecular Hematopoiesis, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. germeshausen.manuela@mh-hannover.de
authors.forename: Manuela
authors.initials: M
authors.lastname: Germeshausen
authors.forename: Cornelia
authors.initials: C
authors.lastname: Zeidler
authors.forename: Manfred
authors.initials: M
authors.lastname: Stuhrmann
authors.forename: Marina
authors.initials: M
authors.lastname: Lanciotti
authors.forename: Matthias
authors.initials: M
authors.lastname: Ballmaier
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D002648:Child; D005838:Genotype; D005952:Glucose-6-Phosphatase / Q000235:genetics*; D006801:Humans; D009154:Mutation; D009503:Neutropenia / Q000151:congenital* / Q000235:genetics
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C104759:HAX1 protein, human; D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human