title: Leaky phenotype of X-linked agammaglobulinaemia in a Japanese family.
abstract: X-linked agammaglobulinaemia (XLA) is an inherited immunodeficiency that is caused by a block in early B-cell differentiation. Whereas early B precursors in the bone marrow are present in substantial numbers, XLA-affected individuals have dramatically reduced numbers of circulating mature B cells, plasma cells and immunoglobulins of all isotypes. We report on a Japanese family with 3 XLA patients, in whom the serum immunoglobulin levels and number of B cells showed a significant difference among them in spite of harbouring the same splice donor site mutation in the BTK gene. We developed concise method for detection of this mutation, which is helpful for discovering the carrier. Patient 2 showed a significant serum immunoglobulin levels of all isotypes, including allergen-specific IgE. Expression of a normal and truncated size BTK gene was detected in patient 2's peripheral blood mononuclear cells (PBMCs). Expression of BTK protein was also detected in some B cells. These results suggest that the leaky phenotype in patient 2 was caused in part by the expression of a normal BTK gene transcript. The increased frequency of infection with age expanded the number of B cells with normal BTK gene expression and produced the serum immunoglobulin, including IgE.
authors.affiliation: Department of Paediatrics, Graduate School of Medicine, Gifu University, Gifu, Japan. hideo@cc.gifu-u.ac.jp
authors.forename: H
authors.initials: H
authors.lastname: Kaneko
authors.forename: N
authors.initials: N
authors.lastname: Kawamoto
authors.forename: T
authors.initials: T
authors.lastname: Asano
authors.forename: Y
authors.initials: Y
authors.lastname: Mabuchi
authors.forename: H
authors.initials: H
authors.lastname: Horikoshi
authors.forename: T
authors.initials: T
authors.lastname: Teramoto
authors.forename: E
authors.initials: E
authors.lastname: Matsui
authors.forename: M
authors.initials: M
authors.lastname: Kondo
authors.forename: T
authors.initials: T
authors.lastname: Fukao
authors.forename: K
authors.initials: K
authors.lastname: Kasahara
authors.forename: N
authors.initials: N
authors.lastname: Kondo
mesh_terms: D000328:Adult; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000235:genetics* / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D005192:Family Health; D005260:Female; D015870:Gene Expression / Q000235:genetics; D008040:Genetic Linkage / Q000235:genetics*; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D007564:Japan; D007963:Leukocytes, Mononuclear / Q000276:immunology; D018655:Lymphocyte Count / Q000379:methods; D008297:Male; D009154:Mutation; D010375:Pedigree; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics
chemical_list: D007136:Immunoglobulins; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human