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 test:testosterone 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.
ABSTRACT
Objective To describe a case of female sexual abnormality with 46, XX caused by an androgen-producing adrenocortical tumor and to explore the mechanism of abnormal androgen secretion from the tumor. Methods The tumor tissues as the experimental group were compared with the normal adrenal tissue. The LH/human chorionic gonadotropin ( hCG) receptor was determined by immunohistochemisty, the activity of 3β-hydroxysteroid dehydrogenase ( 3β-HSD ) , 17α-hydroxylase ( CYP17 ) , and 17β-hydroxysteroid oxidoreductase ( 17β-HSD ) by enzyme linked immunosorbent assay(ELISA) and the expression of mRNA of 3β-HSD2, 17β-HSDB3, CYP17, and LH/hCG receptor by real-quantitative polymerase chain reaction ( RQ-PCR ) . Results The immunohistochemisty results showed that the LH/hCG receptor was negative in the experiment group, but positive in control. The activity of 3β-HSD and CYP17 of the experiment group was higher than that in the control (P<0. 01), while the activity of 17β-HSD was lower(2 638. 798±70. 551 vs 9 148. 174±382. 836, P<0. 01) according to ELISA results. The relative contentof3β-HSD2mRNAoftheexperimentgroupwashigherthanthatinthecontrol(P<0.05),andtherelative content CYP17 mRNA of the experiment group was much higher than that in the control (P<0. 01). However, the relative content of 17β-HSDB3 mRNA and LH/hCG receptor mRNA were much lower than those in the control ( P<0. 01) by RQ-PCR. Conclusion Sexual abnormality and virilization could be caused by the excessive androgen secreted by androgen-producing adrenocortical tumor, which is an extremely rare disease. The mechanism of the secretion of androgen from the tumor remains unknown so far. It may be related to the increased activity of 3β-HSD and CYP17, but has no relationship with the expression of LH/hCG receptor.
ABSTRACT
The transient surge in the hypothalamic GnRH pulse generator-pituitary gonadotropin-gonadal apparatus,sometimes called the minipuberty of early infancy, is associated with special secretion pattern of many sex hormones. This period is thought to be an important stage for sex development, and provides clinicians early evidences to diagnose sexual abnormality diseases. This review summarizes the formation and characteristic of minipuberty,and the mechanism of its abnormal hormone secretion leading to sexual abnormality, and thus focus on the value of minipuberty for early diagnosis of sexual abnormality diseases.
ABSTRACT
Objective TO Provide information for clinical diagnosis and study the mechanism of sexual abnormality . Methods 6 cases of sexual abnormality were detected with PCR amplification and DNA sequencing techniques.ResultsSRY gene was positive in 45,XO male and 46,XY female whose DNA sequence of conserved region had no mutation.SRY gene was negative in 46,Xxmale.Three46,XY males with sexual abnormality showed SRY positive.Conclusions The sexual abnormality of 45,Xomale was caused by SRY positive.Conclusions The sexual abnormality of 45,XOmale was caused by SRY gene translocation .Sexual reverse infemale was caused by gene conseved region mutation but in male it might be caused by sexual related gene mutation on chromasome.