A double nucleotide insertion-induced frame-shift mutation of the androgen receptor gene in a familial complete androgen insensitivity syndrome

Objective

A wide spectrum of androgen receptor (AR) gene mutations has been reported in complete androgen insensitivity syndrome (CAIS). The molecular basis of androgen resistance was investigated in a female with familial CAIS.

Study design

AR gene and protein were investigated by PCR and direct sequencing and Western immunoblotting, respectively.

Results

Sequencing analysis of DNA of the patient identified a double nucleotide insertion in exon 4 that results in the frame-shift leading to premature terminal signal in the beginning of exon 6. This mutation predicted the synthesis of a truncated AR that lacks the entire ligand-binding molecules. Immunoblotting analysis of the gonad removed from the patient detected the mutated AR protein of 94 kDa. Positive control revealed the normal apparent molecular mass of 110 kDa. DNA sequencing of her mother demonstrated the presence of both canonical and mutated sequences in the exon 4 through 8.

Conclusion

These findings suggested that the previously undescribed insertion mutation in the AR gene is the cause of CAIS in this family.