A novel mutation of the androgen receptor gene causes androgen insensitivity syndrome:a case report and literature review / 中华实用儿科临床杂志

ABSTRACT

Objective To explore the mutation of androgen receptor(AR)gene in a patient with 46,XY disorder of sex development(DSD)and to improve the diagnostic level and understanding of androgen insensitivity syndrome(AIS).Methods The clinical data of the child was analyzed,including physical examination,relevant laboratory examination,karyotype,pelvic B ultrasound,pelvic magnetic resonance imaging(MRI)and AR gene mutation.The peripheral blood of the child and his parents were drawn,and peripheral blood DNA was extracted.The polymerase chain reaction(PCR)-DNA sequencing method was used to amplify all exons of the AR gene in the child and his parents.Then,they were directly sequenced.Results A 7-years and 2-months old child who suffered from DSD,revealed physical examination that the child had normal female external genitalia,as the clitoris length was 2.0 cm×0.8 cm,with visible vaginal opening,and there were masses at bilateral inguinal region,with a size of 1.5 cm×0.8 cm.The results of human chorionic gonadotropin(HCG)stimulation testtestosterone was 0 nmol/L,androstenedione was 1.78 nmol/L,dihydrotestosterone was 0.07 nmol/L before HCG was injected;but testosterone was 4.69 nmol/L,androstenedione was 2.10 nmol/L,dihydrotestosterone was 0.33 nmol/L after HCG was injection.Sex chromosome analysis reported 46,XY karyotype.Pelvic B ultrasound revealed the absence of a uterus and ovaries and the presence of bilateral testes like gonad at each side of internal inguinal ring,with a size of 1.4 cm×1.0 cm×0.8 cm in the left,1.5 cm×0.7 cm×0.8 cm in the right;but the kidney,ureter,urinary bladder,adrenal gland and retroperitoneal for B ultrasound revealed no abnormality.Pelvic MRI(non-enhanced and enhanced)showed the presence of a blind ending vagina between rectum and urinary bladder(40 mm in depth)and the absence of uterus and ovarian tissue.DNA sequencing found one c.1685T>C heterozygous mutation(p.Ile562Thr)on exon 2 of AR gene in the child.But retrieving and summarzing documents of the domestic and foreign information databases and websites,the locus mutation of AR gene had never been reported.The structure prediction of the mutated protein(Polyohen2 and SIFT software)was significantly changed.By verifying the locus site of the parents of this child,it was found that his mother carried the same mutation,but his father was found to be normal.Conclusions A c.1685 T>C mutation(p.Ile562Thr)on exon 2 of AR gene is a novel mutation.Combined with the patient's clinical manifestations and computer prediction results,it may suggest that the novel mutation of AR gene can lead to the occurrence of AIS.