title: Detection of Bruton's tyrosine kinase mutations in hypogammaglobulinaemic males registered as common variable immunodeficiency (CVID) in the Japanese Immunodeficiency Registry.
abstract: CVID is frequently diagnosed in male and female individuals with hypogammaglobulinaemia of unknown aetiology. To examine the possibility that sporadic male cases with X-linked agammaglobulinaemia (XLA), which is caused by mutations in the Bruton's tyrosine kinase (Btk) gene, might be misregistered as having CVID, we employed a flow cytometric test to identify XLA in hypogammaglobulinaemic males registered as CVID in the Japanese Immunodeficiency Registry. From 30 male cases registered as having CVID between 1992 and 1998, we selected 21 males with low or unreported peripheral B cell counts. Blood samples could be obtained from 11 patients and their mothers. Using flow cytometric analysis, the Btk-deficient status in monocytes was demonstrated in seven out of nine cases with decreased numbers of peripheral B cells. The diagnosis of XLA was confirmed in each of the seven patients by demonstration of Btk gene mutations in the patients or cellular mosaicism in the mother. This study demonstrates misregistration of XLA as CVID.
authors.affiliation: Department of Paediatrics, Faculty of Medicine, Toyama Medical and Pharmaceutical University, Toyama, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kanegane
authors.forename: S
authors.initials: S
authors.lastname: Tsukada
authors.forename: T
authors.initials: T
authors.lastname: Iwata
authors.forename: T
authors.initials: T
authors.lastname: Futatani
authors.forename: K
authors.initials: K
authors.lastname: Nomura
authors.forename: J
authors.initials: J
authors.lastname: Yamamoto
authors.forename: T
authors.initials: T
authors.lastname: Yoshida
authors.forename: K
authors.initials: K
authors.lastname: Agematsu
authors.forename: A
authors.initials: A
authors.lastname: Komiyama
authors.forename: T
authors.initials: T
authors.lastname: Miyawaki
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes; D002469:Cell Separation; D017074:Common Variable Immunodeficiency / Q000175:diagnosis / Q000235:genetics / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D008040:Genetic Linkage; D006801:Humans; D007564:Japan; D018655:Lymphocyte Count; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D012042:Registries; D014960:X Chromosome
chemical_list: D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human