title: XLA patients with BTK splice-site mutations produce low levels of wild-type BTK transcripts.
abstract: X-linked agammaglobulinemia is caused by mutations in the BTK gene, which result in a precursor B-cell differentiation arrest in the bone marrow and the absence of or strongly reduced B lymphocytes in blood. We identified a patient with a mild clinical phenotype, low numbers of B lymphocytes, and a splice-site mutation in the BTK gene. The precursor B-cell compartment in the bone marrow of this patient was almost identical to that in healthy children. Using real-time quantitative polymerase chain reaction, we were able to detect low levels of wild-type BTK transcripts in his granulocytes. Therefore, we speculated that wild-type BTK transcripts might be responsible for a milder clinical and immunological phenotype, as has been shown in several other diseases. Consequently, we quantified the expression of wild-type BTK transcripts in granulocytes of eight additional patients with splice-site mutations and compared their phenotypes with 17 patients with other types of BTK mutations. In these eight patients, the presence of low levels of wild-type BTK transcripts did not show a clear correlation with the percentage, absolute number, or immunophenotype of B lymphocytes nor with age or serum immunoglobulin levels at diagnosis. Nevertheless, we postulate that the presence of wild-type BTK transcripts can be one of the many factors that influence the clinical and immunological phenotype in X-linked agammaglobulinemia.
authors.affiliation: Department of Immunology, Erasmus MC, University Medical Center Rotterdam, The Netherlands.
authors.forename: Jeroen G
authors.initials: JG
authors.lastname: Noordzij
authors.forename: Sandra
authors.initials: S
authors.lastname: de Bruin-Versteeg
authors.forename: Nico G
authors.initials: NG
authors.lastname: Hartwig
authors.forename: Corry M R
authors.initials: CM
authors.lastname: Weemaes
authors.forename: Egbert J A
authors.initials: EJ
authors.lastname: Gerritsen
authors.forename: Eva
authors.initials: E
authors.lastname: Bernatowska
authors.forename: Stefaan
authors.initials: S
authors.lastname: van Lierde
authors.forename: Ronald
authors.initials: R
authors.lastname: de Groot
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
mesh_terms: D000293:Adolescent; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000361:Agammaglobulinemia / Q000201:enzymology / Q000235:genetics* / Q000276:immunology; D017398:Alternative Splicing; D002648:Child; D041321:Chromosomes, Human, X; D004274:DNA, Recombinant; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D008297:Male; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism
chemical_list: D004274:DNA, Recombinant; D012333:RNA, Messenger; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human