title: Mutation analysis of the gene encoding Bruton's tyrosine kinase in a family with a sporadic case of X-linked agammaglobulinemia reveals three female carriers.
abstract: Bruton's tyrosine kinase (Btk) has been identified as the protein responsible for the primary immunodeficiency X-linked agammaglobulinemia (XLA). We and others have cloned the gene for Btk and recently reported the genomic organization. Nineteen exons were positioned within the 37 kb gene. With the sequence data derived from our genomic map, we have designed a PCR based assay to directly identify mutations of the Btk gene in germline DNA of patients with XLA. In this report, the assay was used to analyze a family with a sporadic case of XLA to determine if other female relatives carry the disease. A four base-pair deletion was found in the DNA of the affected boy and was further traced through three generations. With the direct identification of the mutations responsible for XLA, we can now diagnose conclusively the disease and identify the immunologically normal female carriers. This same technique can easily be applied to prenatal diagnosis in families where the mutation can be identified.
authors.affiliation: Department of Immunology/Microbiology, Rush Medical School, Chicago, IL 60612, USA.
authors.forename: T L
authors.initials: TL
authors.lastname: Hagemann
authors.forename: A H
authors.initials: AH
authors.lastname: Assa'ad
authors.forename: S P
authors.initials: SP
authors.lastname: Kwan
mesh_terms: D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology* / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002675:Child, Preschool; D004247:DNA / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D006580:Genetic Carrier Screening; D008040:Genetic Linkage; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D011505:Protein-Tyrosine Kinases / Q000235:genetics*; D017384:Sequence Deletion; D014960:X Chromosome / Q000235:genetics*
chemical_list: D004247:DNA; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human