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Blood, 15 May 2008, Vol. 111, No. 10, pp. 4954-4957. Prepublished online as a Blood First Edition Paper on March 12, 2008; DOI 10.1182/blood-2007-11-120667. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2007-11-120667v1 111/10/4954    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Germeshausen, M. Articles by Klein, C. Search for Related Content PubMed PubMed Citation Articles by Germeshausen, M. Articles by Klein, C. Related Collections Hematopoiesis and Stem Cells Phagocytes Brief Reports Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Brief Report Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype-phenotype associations Manuela Germeshausen1, Magda Grudzien2, Cornelia Zeidler1, Hengameh Abdollahpour1, Sevgi Yetgin3, Nima Rezaei4, Matthias Ballmaier1, Bodo Grimbacher2,5, Karl Welte1, and Christoph Klein1 1 Department of Pediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany; 2 Department of Clinical Immunology, University Hospital Freiburg, Freiburg, Germany; 3 Department of Pediatric Hematology, Hacettepe University, Children's Hospital, Ankara, Turkey; 4 Immunology, Asthma and Allergy Research Institute, Medical Sciences/University of Tehran, Tehran, Iran; and 5 Department of Immunology and Molecular Pathology, Royal Free Hospital and University College Medical School, London, United Kingdom Homozygous mutations in HAX1 cause an autosomal recessive form of severe congenital neutropenia (CN). By screening 88 patients with CN, we identified 6 additional patients with HAX1 mutations carrying 4 novel mutations. Of these, 2 affect both published transcript variants of HAX1; the other 2 mutations affect only transcript variant 1. Analysis of the patients' genotypes and phenotypes revealed a striking correlation: Mutations affecting transcript variant 1 only were associated with CN (23 of 23 patients), whereas mutations affecting both transcript variants caused CN and neurologic symptoms, including epilepsy and neurodevelopmental delay (6 of 6 patients). In contrast to peripheral blood, transcript variant 2 was markedly expressed in human brain tissue. The clinical phenotype of HAX1 deficiency appears to depend on the localization of the mutation and their influence on the transcript variants. Therefore, our findings suggest that HAX1 isoforms may play a distinctive role in the neuronal system. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. Klein Molecular basis of congenital neutropenia Haematologica, October 1, 2009; 94(10): 1333 - 1336. [Full Text] [PDF] N Ishikawa, S Okada, M Miki, K Shirao, H Kihara, M Tsumura, K Nakamura, H Kawaguchi, M Ohtsubo, S Yasunaga, et al. Neurodevelopmental abnormalities associated with severe congenital neutropenia due to the R86X mutation in the HAX1 gene J. Med. Genet., December 1, 2008; 45(12): 802 - 807. [Abstract] [Full Text] [PDF]

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