Mutation detection in the X-linked agammaglobulinemia gene, BTK, using single strand conformation polymorphism analysis

The gene defective in X-linked agammaglobulinemia (XLA) has recently been isolated and identified as btk, a non-receptor protein tyrosine kinase. We have utilized the technique of single strand conformation polymorphism (SSCP) analysis for the btk gene to identify mutations in XLA patients. The btk Bene in affected boys from 10 families was analysed and mutations were identified in eight cases; seven of these were point mutations and one was a small insertion. The mutations were found throughout the gene coding region. Six of the patients have classical XLA and two have less severe forms of the disease. We have also identified a polymorphism at nucleotide position 2031. This technique will allow us to provide more accurate diagnoses of the disease and to determine the nature of the functional defects in the btk gene in these families.