Digenic mutations in severe congenital neutropenia.
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.
Germeshausen
Manuela
M
Department of Pediatric Hematology and Oncology/Molecular Hematopoiesis, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. germeshausen.manuela@mh-hannover.de
Zeidler
Cornelia
C
Stuhrmann
Manfred
M
Lanciotti
Marina
M
Ballmaier
Matthias
M
Welte
Karl
K
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
D048868:Adaptor Proteins, Signal Transducing; C104759:HAX1 protein, human; D005952:Glucose-6-Phosphatase; C492193:G6PC3 protein, human