Androgen receptor gene mutation identified by PCR-SSCP and sequencing in 4patients with complete androgen insensitivity syndrome

To study the genetic defect of the human androgen receptor (hAR) gene in th e complete androgen insensitivity syndrome (CAIS), we amplified each of the eight exons by PCR in genomic DNA extracted from the paraffin blocks of th e resected gonads. We analyzed using SSCP. and directly sequenced the abnor mally shifted bands. Mutations were found in 4 cases of CAIS. Patient 1 car ried a point mutation; a G to A transition in exon 7 resulted in a change f rom arginine to glutamine at codon 831. Patient 2 carried a point mutation; a C to T transition in exon 7 resulted in a change from arginine to stop a t codon 831. Patient 3 carried a point mutation and deletion in exon 7. A p oint mutation was an A to G transition that caused a glutamine to be substi tuted for the asparagine present at codon 819. A deletion of a G at codon 8 20 resulted in a frameshift and consequently in the introduction of a prema ture stop at codon 821. Patient 4 carried a mutation in 5' splice donor sit e of intron 7; a G to T transition might have caused an abnormal splicing o f the exon 7. All of the mutations were found in exon 7. These mutations of hAR gene might be related to the pathogenesis of CAIS.