A novel single basepair insertion in exon 6 of the Bruton's tyrosine kinase (Btk) gene from a Japanese X-linked agammaglobulinemia patient with growth hormone insufficiency.

A novel insertion mutation in exon 6 of the Btk gene was detected in a 17 year-old XLA patient with GH insufficiency. We synthesized cDNA from leukocyte total RNA and amplified every region of the Btk-coding sequence. Sequencing of cDNA fragments revealed a single basepair insertion mutation at codon 157 in exon 6 (CAG-->CAAG) which leads to premature termination at codon 193 in exon 7. To confirm the results, we also performed a PCR-DdeI digestion analysis using leukocyte genomic DNA. The PCR product from the patient's genomic DNA was uncleaved with DdeI, as expected. PCR-DdeI digestion analysis of the family members showed that the mother and elder sister were carriers with the mutation and that the younger sister did not carry the mutation.