The Clinical Phenotypes And Etiological Study Of Gonadal Dysgenesis Or AIS Children

Objective To study the clinical manifestations and serum sex hormone changes of 46,XY patients with abnormal testicular development.Besides,the clinical significance of serum AMH and INHB was also important in the study.Besides,we focused on the relation between genotypes of GATA4,SRY,SOX9,DAX1,FGF9,DMRT1 and CBX2 and phenotypes.Methods We evaluate the clinical manifestations by collecting the related medical history and examination results.We detect serum sex hormones,including AMH and INHB.DNA were extracted from the patient’s blood samples.Then the design and synthesis of primers of related genes were made for PCR amplifications.After that PCR amplifications were sequenced and the results were analyzed finally by us.Results Vanishing testes(60%)are more common in 46,XY patients with abnormal testicular development compared to patients with testicular cords(26.7%)or patients with undescended testes(13.3%).Serum AMH and INHB were unable to be detected in 11 patients.Three non-SNP missense mutations were found in the study,namely the GATA4 gene mutation c.648 G>C(p.E216D),the NR5A1 mutation c.1350 C>G(p.N450K)and the SOX9 gene mutation c.1166 C>T(p.P389L).9 patients have NR5A1 gene variation c.G437C(p.G146A)and 7 patients have DMRT1 gene variation c.133 T>A(p.S45T),both of the variations are SNPs.This suggest the GATA4 gene mutation c.648 G>C(p.E216D),the NR5A1 mutation c.1350 C>G(p.N450K)and the SOX9 gene mutation c.1166 C>T(p.P389L)may be related with phenotypes of the patients.Conclusion(1)Vanishing testes and cord-like testicular are more common clinical manifestations of 46,XY patients with abnormal testicular development.(2)Detection of INHB and AMH combined with testosterone levels before and after HCG stimulation test contributes to envaluate testicular function and the presence or absence of testicle tissue.(3)GATA4 gene mutation c.648 G>C(p.E216D),NR5A1 gene mutation c.1350 C>G(p.N450K)and SOX9 gene mutation c.1166 C>T(p.P389L)may lead to abnormal testicular development in 46,XY patients.Mutation c.G437C(p.G146A)of NR5A1 gene in 9 patients and mutation c.133T>A(p.S45T)of DMRT1 gene in 7 patients do not pathogenic.Objectives To investigate the relationships between genotypes of genetic changes of AR and SRD5A2 and phenotypes of 13 patients with androgen insensitivity syndrome.Methods We evaluate the clinical manifestations by collecting the related medical history and examination results.DNA were extracted from the patient’s blood samples.Then the design and synthesis of primers of related genes were made for PCR amplifications.After that PCR amplifications were sequenced and we analyze the results finally.Results There were 6 kinds of AR gene missense mutations in 13 patients.They are c.2107T>C(p.S703P),c.528C>A(p.S176R),c.170T>A(p.L57Q),c.2567G>A(p.R856H),c.2740C>G(p.P914A)and c.2351A>G(p.Q784R).c.2107T>C(p.S703P),c.2740C>G(p.P914A)and c.2351A>G(p.Q784R)are new mutations.Pathogenic SRD5A2 gene mutations were not found in 13 patients.Besides,CAG duplications abnormal changes in the AR gene were also found in three patients.Patients with AIS may exhibit female genital mutilation,cryptorchidism and hypospadias in the study.No AR missense mutations were found in the normal control group and 15 patients with nonpathogenic SRD5A2 gene variations were found in the normal control group.Conclusions(1)Six missense mutations c.2107T>C(p.S703P),c.528C>A(p.S176R),c.170T>A(p.L57Q),c.2567G>A(p.R856H),c.2740C>G(p.P914A)and c.2351 A>G(p.Q784R)may cause AIS.(2)Three new mutations c.2107T>C(p.S703P),c.2740C>G(p.P914A)and c.2351A>G(p.Q784R)may lead to complete androgen insensitivity syndrome.(3)CAG repeats abnormal changes of the AR gene may be one of the causes of those patients without AR mutations.