Universität zu Köln

Boztug, Kaan ORCID: 0000-0001-8387-9185, Ding, Xiao-Qi, Hartmann, Hans, Ziesenitz, Lena, Schaeffer, Alejandro A., Diestelhorst, Jana, Pfeifer, Dietmar, Appaswamy, Giridharan, Kehbel, Sonja, Simon, Thorsten, Al Jefri, Abdullah, Lanfermann, Heinrich and Klein, Christoph (2010). HAX1 Mutations Causing Severe Congenital Neuropenia and Neurological Disease Lead to Cerebral Microstructural Abnormalities Documented by Quantitative MRI. Am. J. Med. Genet. A, 152A (12). S. 3157 - 3164. HOBOKEN: WILEY. ISSN 1552-4833

Full text not available from this repository.

Abstract

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. (C) 2010 Wiley-Liss, Inc.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Boztug, Kaan UNSPECIFIED orcid.org/0000-0001-8387-9185 UNSPECIFIED Ding, Xiao-Qi UNSPECIFIED UNSPECIFIED UNSPECIFIED Hartmann, Hans UNSPECIFIED UNSPECIFIED UNSPECIFIED Ziesenitz, Lena UNSPECIFIED UNSPECIFIED UNSPECIFIED Schaeffer, Alejandro A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Diestelhorst, Jana UNSPECIFIED UNSPECIFIED UNSPECIFIED Pfeifer, Dietmar UNSPECIFIED UNSPECIFIED UNSPECIFIED Appaswamy, Giridharan UNSPECIFIED UNSPECIFIED UNSPECIFIED Kehbel, Sonja UNSPECIFIED UNSPECIFIED UNSPECIFIED Simon, Thorsten UNSPECIFIED UNSPECIFIED UNSPECIFIED Al Jefri, Abdullah UNSPECIFIED UNSPECIFIED UNSPECIFIED Lanfermann, Heinrich UNSPECIFIED UNSPECIFIED UNSPECIFIED Klein, Christoph UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-491046
DOI:	10.1002/ajmg.a.33748
Journal or Publication Title:	Am. J. Med. Genet. A
Volume:	152A
Number:	12
Page Range:	S. 3157 - 3164
Date:	2010
Publisher:	WILEY
Place of Publication:	HOBOKEN
ISSN:	1552-4833
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language UNFOLDED PROTEIN RESPONSE; NEUTROPHIL ELASTASE; LINKAGE ANALYSIS; GENE; DEFICIENCY; APOPTOSIS; KOSTMANN; FAMILY; TISSUE Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49104