A Molecular Approach in A Case Series of 46, XY Gonadal Dysgenesis Patients.

Background: 46,XY Gonadal dysgenesis (46,XY GD) is a rare congenital disorder with no apparent incidence, thus current knowledge about age and clinical presentation at diagnosis is sparse. 46,XY GD results from alteration in genes involved in testis differentiation and thereby affect the development of the internal and external genital organs. In most of the cases, the underlying molecular mechanism remains elusive. The aim of this study is to identify the genetic causes of 46,XY GD pa-tients.Materials and Methods: A retrospective study was performed of patients with female phenotype and 46,XY karyotype. They were assessed preoperatively with ultrasonography, hormo-nal examination of the gonadotropins FSH and LH as well as testosterone, and histopathological reports. We performed se-quence analyses of the SRY, NR5A1, and ZFPM2 genes also deletion in SOX9 promoter will be done by qPCR Results: The series consisted of 12 patients, all with female gender and non-palpable gonads. Ambiguous or female exter-nal genitalia, primary amenorrhea, absence or disorder of Mul-lerian structure, delayed puberty and infertility are important manifestations of these patients. We analyzed the clinical inves-tigations; all of the patients during puberty had a strong rise of FSH, LH levels, and testosterone levels were reduced. Patients had a gonad or gonads that were described as small or in-fantal . We did not observe mutation in the SRY gene likewise, specific variation in NR5A1 and ZFPM2 were not reported.Conclusion: We describe the first Iranian 46,XY GD patients. The presentation of gonadal dysgenesis is during pubertal years. Follow-up laboratory investigations showed decreased testosterone levels, despite elevated gonadotropin levels, in-dicating gonadal dysfunction. We conclude that while SRY is an essential transcription factor of testicle development, there are many genes involved in sexual development. Futher clinical studies are required for better molecular diagnosis.

کلیدواژه ها:

46 ، XY Gonadal Dysgenesis ، Testis Development ، SRY