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Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation
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From the Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan; Department of Pediatrics, Faculty of Medicine Toyama Medical and Pharmaceutical University, Toyama, Japan; Division of Molecular Population Genetics, Department of Molecular Genetics, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan; Departments of Pediatrics, Kyushu Kouseinenkin Hospital, Kitakyushu, Japan; and Department of Molecular Medicine, Osaka University Medical School, Osaka, Japan.

  We analyzed the cause of agammaglobulinemia in a girl whose father had been diagnosed as having X-linked agammaglobulinemia (XLA). Flow cytometric analysis revealed the lack of peripheral B cells with the block of B-cell differentiation in the stages between pro-B cells and pre-B cells in the bone marrow, and the defect of the Bruton tyrosine kinase (BTK) expression on monocytes. We found a BTK gene mutation in the first single base pair of intron 11 in her father and heterozygous mutation in the patient at the site. Sequence analysis of abnormally smaller-sized polymerase chain reaction (PCR) products of cDNA confirmed splicing abnormalities due to the mutation. Maternally derived X chromosome was exclusively inactivated in peripheral blood and oral mucosal cells. This is the first report of female XLA caused by heterozygous BTK gene abnormality and extreme nonrandom inactivation of X chromosome on which normal BTK gene is located.



  
《血液学杂志》2004年1月第103卷第1期