How to Cite this Article: Boztug K, Ding X-Q, Hartmann H, Ziesenitz L, Schäffer AA, Diestelhorst J, Pfeifer D, Appaswamy G, Kehbel S, Simon T, Al Jefri A, Lanfermann H, Klein C. 2010. HAX1 Mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI. Am J Med Genet Part A 152A:3157–3163.
Article first published online: 24 NOV 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part A
Volume 152A, Issue 12, pages 3157–3163, December 2010
How to Cite
Boztug, K., Ding, X.-Q., Hartmann, H., Ziesenitz, L., Schäffer, A. A., Diestelhorst, J., Pfeifer, D., Appaswamy, G., Kehbel, S., Simon, T., Al Jefri, A., Lanfermann, H. and Klein, C. (2010), HAX1 mutations causing severe congenital neuropenia and neurological disease lead to cerebral microstructural abnormalities documented by quantitative MRI. Am. J. Med. Genet., 152A: 3157–3163. doi: 10.1002/ajmg.a.33748
Kaan Boztug and Xiao-Qi Ding contributed equally to this work.
- Issue published online: 24 NOV 2010
- Article first published online: 24 NOV 2010
- Manuscript Accepted: 5 SEP 2010
- Manuscript Received: 9 JUN 2010
- Clotten Stiftung
- Fritz-Thyssen Foundation
- severe congenital neutropenia;
- quantitative MRI;
Biallelic mutations in the gene encoding HCLS-associated protein X-1 (HAX1) cause autosomal recessive severe congenital neutropenia (SCN). Some of these patients have neurological abnormalities including developmental delay, cognitive impairment, and/or epilepsy. Recent genotype–phenotype studies have shown that mutations in HAX1 affecting transcripts A (NM_006118.3) and B (NM_001018837.1) cause the phenotype of SCN with neurological impairment, while mutations affecting isoform A but not B lead to SCN without neurological aberrations. In this study, we identified a consanguineous family with two patients suffering from SCN and neurological disease caused by a novel, homozygous genomic deletion including exons 4–7 of the HAX1 gene. Quantitative MRI analyses showed generalized alterations in cerebral proton density in both of the patients, as well as in an additional unrelated patient with another HAX1 mutation (Arg86X) known to be associated with neurological manifestations. This study provides first in vivo evidence of aberrant neuroimaging findings associated with HAX1 deficiency in SCN patients. © 2010 Wiley-Liss, Inc.