Exploration Of Genetic Etiology For30Patients With Disorders Of Sex Development

Objective:The study is aimed to investigate the genetic etiology of30patients with disorders of sex development (DSD), standardize the genetic diagnosis system of sex chromosome DSD,46,XY DSD and46,XXDSD.Methods:30patients with DSD were recruited and calassified by their gonad assessment, endocrine hormone detection, imaging tests, family history,combined the clinical phenotypes and karyotype.The Fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA), polymerase chain reaction (PCR) and sequencing were applied to analyze the molecular mechanism of the disease.Results:(1) Among30patients with DSD,2patients were sex chromosome DSD,16patients were46,XX DSD,12patients were46,XY DSD.(2) Two patients of sex chromosome DSD were mosaic carrying isodicentromere Ychromosome with female phenotype.(3) Among16patients of46,XX DSD,15patients had SRY gene without any mutation; One patient had no SRY gene was negative, and gender related gene copy number abnormities had not been found by MLPA.(4) Among12patients of46,XX DSD,5patients had AR gene mutations,2patients had SRD5A2gene mutations.Conclusion:(1) The low proportion of the functional Y chromosome may be an etiological factor of the patients carrying idic (Y) with female phenotype;(2) The primary causes of46,XX DSD is the hidden SRY gene translocated to the X chromosome. There is an alternative way beyond the traditional gender determination in the patient of male phenotype with SRY negative;(3) For the etiologies patients with 46,XY DSD, androgen insensitivity syndrome and some hypospadias could be diagnosed, but the others were still unknown.