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. 2010 Jul;95(7):1207-10.
doi: 10.3324/haematol.2009.017665. Epub 2010 Mar 10.

Digenic mutations in severe congenital neutropenia

Manuela Germeshausen  1 , Cornelia Zeidler, Manfred Stuhrmann, Marina Lanciotti, Matthias Ballmaier, Karl Welte
Affiliations

Digenic mutations in severe congenital neutropenia

Manuela Germeshausen et al. Haematologica. 2010 Jul.

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.

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