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Digenic mutations in severe congenital neutropenia

¹ Dept. of Molecular Hematopoiesis, Hannover Medical School, Hannover, Germany
² Institute of Human Genetics, Hannover Medical School, Hannover, Germany
³ Dept. of Pediatric Hematology and Oncology, Giannina Gaslini Institute, Genoa, Italy

Correspondence: Manuela Germeshausen, Dept. of Molecular Hematopoiesis, Medizinische Hochschule Hannover, Carl-Neuberg-Str. 1, D-30625 Hannover, Germany. E-mail: germeshausen.manuela{at}mh-hannover.de

ABSTRACT

Severe congenital neutropenia (CN) is 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 CN 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 four CN 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 two 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 CN patients.