title: Female agammaglobulinemia due to the Bruton tyrosine kinase deficiency caused by extremely skewed X-chromosome inactivation.
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.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. takadah@pediatr.med.kyushu-u.ac.jp
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Takada
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kanegane
authors.forename: Akihiko
authors.initials: A
authors.lastname: Nomura
authors.forename: Ken
authors.initials: K
authors.lastname: Yamamoto
authors.forename: Kenji
authors.initials: K
authors.lastname: Ihara
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Takahashi
authors.forename: Satoshi
authors.initials: S
authors.lastname: Tsukada
authors.forename: Toshio
authors.initials: T
authors.lastname: Miyawaki
authors.forename: Toshiro
authors.initials: T
authors.lastname: Hara
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology; D001483:Base Sequence; D002454:Cell Differentiation; D041321:Chromosomes, Human, X / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D004303:Dosage Compensation, Genetic; D005260:Female; D008040:Genetic Linkage; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D017354:Point Mutation; D011505:Protein-Tyrosine Kinases / Q000172:deficiency* / Q000235:genetics*; D012326:RNA Splicing / Q000235:genetics
chemical_list: D018076:DNA, Complementary; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human