[HTML][HTML] Digenic mutations in severe congenital neutropenia

M Germeshausen, C Zeidler, M Stuhrmann… - …, 2010 - ncbi.nlm.nih.gov
M Germeshausen, C Zeidler, M Stuhrmann, M Lanciotti, M Ballmaier, K Welte
haematologica, 2010ncbi.nlm.nih.gov
Severe congenital neutropenia a clinically and genetically heterogeneous disorder.
Mutations in different genes have been described as causative for severe neutropenia, eg
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 …
Abstract
Severe congenital neutropenia a clinically and genetically heterogeneous disorder. Mutations in different genes have been described as causative for severe neutropenia, eg 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.
ncbi.nlm.nih.gov