MUTATIONAL CHARACTERISTICS OF PATIENTS WITH X-LINKED AGAMMAGLOBULINEMIA WITH THE CARRIER IDENTIFIED BY GENETIC ANALYSIS

Abstract

Background: X-linked agammaglobulinemia (XLA) is a humoral primary immunodeficiency in which affected patients have very low levels of peripheral B cells and a profound deficiency of all immunoglobulin isotypes. The mutational screening of Bruton ́s tyrosine kinase (BTK) gene could detect XLA as well as its carrier. Materials and methods: In this work, we describe 13 patients with BTK mutations and the carrier status of their family members. DNA was prepared from the patients' peripheral blood cells and RNA from the patients' peripheral blood mononuclear cells. BTK gene analysis was carried out using PCR or RT-PCR followed by sequencing. Results: We identified five patients with missense mutations, five premature stop codons caused by substitutions or frameshifts, one deletion of 23 nucleotides and two with splice site defects. Most of these mutations were located at the kinase domain of BTK and, less frequently, they were found in PH and 271 SH2 domains. BTK mutated alleles was identified in nine women, defining them as XLA carriers. Conclusions: Characterization of the mutations responsible for XLA allowed us to diagnose the disease conclusively and enables subsequent genetic counseling of patients' relatives.