Objective: To study genic mutation of androgen receptor in hypospadias in Chinese.
Methods: Ninety-two patients with hypospadias were selected for the AR gene study (penile 33, scrotal 49, perineal 10; cryptorchidism 15, micropenis 34, indirect hernia 3, augmentation of breast 2, other deformities 8; posses family history 23) while 93 health men as the control. The DNA was collected from 5 ml venous blood by using the method of phenol/chloroform, and quantified with the agarose gel electrophoresis. The 2-8 exons of AR genes were directly sequenced with a PCR technique. The locus of mutation,the change of amino acid caused by genic mutation and the functional influence of target organ were also analyzed.
Results: There were 4 mutations found from the ligand binding domain of AR: exon 4[1 locus:664(ATT-->ACT] and exon 7[3 locuses: 840(CGT-->CAT),855(CGC-->CAC),859(CTC-->CTA)] in experimental group. The amino acid change of Iso664Thr may te the first findings in the world. The mutation of 859(CTC-->CTA) didn't cause the change of the code amino acid. The main clinical symptoms of exon 4[664(ATT-->ACT) were micropenis, slight hypospadias and augmentation of breasts. The exon 7[840(CGT-->CAT), 855(CGC-->CAC)]was showing micropenis and severe hypospadias. The last mutation [859(CTC-->CTA)] of exon 7 showed mild hypospadias.
Conclusions: The rate of exon 2-7 mutations of the androgen receptor was 4.3%. The mutations were concentrated on ligand binding domain(exon 4-7), and the main phenotypes were hypospadias accompanying with micropenis found in our experimental group.