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 b een isolated and identified as btk, a non-receptor protein tyrosine ki nase. We have utilized the technique of single strand conformation pol ymorphism (SSCP) analysis for the btk gene to identify mutations in XL A patients. The btk gene in affected boys from 10 families was analyse d and mutations were identified in eight cases; seven of these were po int 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 identi fied a polymorphism at nucleotide position 2031. This technique will a llow us to provide more accurate diagnoses of the disease and to deter mine the nature of the functional defects in the btk gene in these fam ilies.