Background: X-linked agammaglobulinaemia (XLA) is a rare immunodeficiency disease, and the main clinical symptoms is recurrent severe infections. BTK is the main disease-causing gene, and the genetic mode is X chromosome recessive inheritance. But the current mutations do not fully explain this disorder.
Methods: We detected the percentage of CD19+ B cells and serum immunoglobulin (IgG, IgA, and IgM) levels by Flow cytometer and rate scatter immunoturbidimetry, and investigated the mutation profile of BTK gene through Sanger sequencing and Real- Time PCR in 22 XLA patients.
Results: We described the clinical symptoms and investigated the genetic mutations in 22 XLA patients, and then identified six novel mutations of BTK gene, which included 2 missense mutations (c.23G>T and c.112T>C), 2 frameshift mutations (c.522_523insC and c.1060delA), 1 large deletion (deletion of exon 2 to 5), and 1 splice-site mutation (c.1631+2T>C). Prenatal diagnosis were performed in six families (F10, F11, F15, F18, F20 and F21). F10 was a male fetus without c.922_923delGA mutation; F15 was a male fetus without c.1631+1G>T splicing mutation; F20 was a female fetus without c.1931T>C mutation; and F21 was a male fetus without large deletion mutation. All four fetuses were less likely to become XLA patients in the future. Family 11 and Family 18 were male fetuses with c.1060delA and c.1684C>T mutations, respectively. The pregnant women in F18 chose to terminate the pregnancy, and the F11 chose to continue the pregnancy.
Conclusion: It is noticeable that we confirmed the diagnosis of 22 XLA patients from 22 unrelated families and found six new pathogenic mutations. Prenatal diagnosis was performed in six families. Early genetic diagnosis and routine lifelong immunoglobulin replacement therapy can prevent and treat the infections of the XLA children and save their lives.