A recurrent dominant negative E47 mutation causes agammaglobulinemia and BCR(-) B cells.

ABSTRACT: Approximately 90% of patients with isolated agammaglobulinemia and failure of B cell development have mutations in genes required for signaling through the pre–B cell and B cell receptors. The nature of the gene defect in the majority of remaining patients is unknown. We recently identified 4 patients with agammaglobulinemia and markedly decreased numbers of peripheral B cells. The B cells that could be detected had an unusual phenotype characterized by the increased expression of CD19 but the absence of a B cell receptor. Genetic studies demonstrated that all 4 patients had the exact same de novo mutation in the broadly expressed transcription factor E47. The mutant protein (E555K) was stable in patient-derived EBV-transformed cell lines and cell lines transfected with expression vectors.

SUBMITTER: Boisson B 

PROVIDER: S-EPMC3809807 | biostudies-literature | 2013 Nov

REPOSITORIES: biostudies-literature