Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation

Hidetoshi Takada, Hirokazu Kanegane, Akihiko Nomura, Ken Yamamoto, Kenji Ihara, Yasuhiko Takahashi, Satoshi Tsukada, Toshio Miyawaki, Toshiro Hara

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)185-187
Number of pages3
JournalBlood
Volume103
Issue number1
DOIs
Publication statusPublished - Jan 1 2004

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X Chromosome Inactivation
Agammaglobulinemia
Chromosomes
Cells
B-Lymphoid Precursor Cells
Genes
Fathers
Mutation
B-Lymphocytes
Polymerase chain reaction
X Chromosome
Reaction products
Base Pairing
Introns
Sequence Analysis
Monocytes
Cell Differentiation
Bone
Blood
Complementary DNA

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

Takada, H., Kanegane, H., Nomura, A., Yamamoto, K., Ihara, K., Takahashi, Y., ... Hara, T. (2004). Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation. Blood, 103(1), 185-187. https://doi.org/10.1182/blood-2003-06-1964

Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation. / Takada, Hidetoshi; Kanegane, Hirokazu; Nomura, Akihiko; Yamamoto, Ken; Ihara, Kenji; Takahashi, Yasuhiko; Tsukada, Satoshi; Miyawaki, Toshio; Hara, Toshiro.

In: Blood, Vol. 103, No. 1, 01.01.2004, p. 185-187.

Research output: Contribution to journalArticle

Takada, H, Kanegane, H, Nomura, A, Yamamoto, K, Ihara, K, Takahashi, Y, Tsukada, S, Miyawaki, T & Hara, T 2004, 'Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation', Blood, vol. 103, no. 1, pp. 185-187. https://doi.org/10.1182/blood-2003-06-1964
Takada, Hidetoshi ; Kanegane, Hirokazu ; Nomura, Akihiko ; Yamamoto, Ken ; Ihara, Kenji ; Takahashi, Yasuhiko ; Tsukada, Satoshi ; Miyawaki, Toshio ; Hara, Toshiro. / Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation. In: Blood. 2004 ; Vol. 103, No. 1. pp. 185-187.
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