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Blood, 1 January 2005, Vol. 105, No. 1, pp. 61-66. Prepublished online as a Blood First Edition Paper on August 12, 2004; DOI 10.1182/blood-2004-02-0675. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-02-0675v1 105/1/61    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Wolach, B. Articles by Roos, D. Search for Related Content PubMed PubMed Citation Articles by Wolach, B. Articles by Roos, D. Related Collections Phagocytes Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CLINICAL OBSERVATIONS, INTERVENTIONS, AND THERAPEUTIC TRIALS Unusual late presentation of X-linked chronic granulomatous disease in an adult female with a somatic mosaic for a novel mutation in CYBB Baruch Wolach, Yitshak Scharf, Ronit Gavrieli, Martin de Boer, and Dirk Roos From the Department of Pediatrics and Laboratory for Leukocyte Function, Meir General Hospital, Sapir Medical Center, Kfar Saba, Israel; The Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel; the Department of Internal Medicine, Assaf Harofeh Medical Center, Zerifin, Israel; Sanquin Research at the Central Laboratory of the Netherlands Blood Transfusion Service (CLB), and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, The Netherlands. Most patients with chronic granulomatous disease (CGD) have mutations in the X-linked CYBB gene that encodes gp91phox, a component of the phagocyte NADPH oxidase. The resulting X-linked form of CGD is usually manifested in boys. Rarely, X-CGD is encountered in female carriers with extreme expression of the mutated gene. Here, we report on a woman with a novel mutation in CYBB (CCG[90-92] GGT), predicting Tyr30Arg31 stop, Val in gp91phox, who presented with clinical symptoms at the age of 66. The mutation was present in heterozygous form in genomic DNA from her leukocytes but was fully expressed in mRNA from these cells, indicating that in her leukocytes the X chromosome carrying the nonmutated CYBB allele had been inactivated. Indeed, only 0.4% to 2% of her neutrophils showed NADPH oxidase activity. This extreme skewing of her X-chromosome inactivation was not found in her cheek mucosal cells and is thus not due to a general defect in gene methylation on one X chromosome. Moreover, the CYBB mutation was not present in the DNA from her cheek cells and was barely detectable in the DNA from her memory T lymphocytes. Thus, this patient shows a somatic mosaic for the CYBB mutation, which probably originated during her lifetime in her bone marrow. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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