Abstract: Objective To detect SRY mutation in 46,XY disorder of sex development (46,XY DSD), to analyze SRY mutation frequency, and to summarize the clinical features of the patients with the mutation. Methods A total of 63 46,XY DSD patients admitted to department of endocrinology of Peking Union Medical College Hospital from 2009 to 2014 were enrolled and detailed clinical data were collected. Genomic DNA was extracted from peripheral blood, and SRY was amplified and sequenced. The mutation was identified by comparing with the online database, and the clinical features were analyzed. Results Three novel mutations of SRY gene were detected in 3 of 63 patients (5%). The 3 patients’ social gender were all female and their karyotypes are 46, XY. Vaginal and uterine structures were present. Sex hormone profiles were consistent with hypergonadotropic hypogonadism. The 3 novel mutations were Pro131His, R76C and L35Afs*25. The former two were mutations in the nuclear localization signal regions of HMG box and highly-conservative amino acids were affected. The latter one was a frameshift mutation resulting in deletion of the entire HMG box. All These were presumably affecting the functional domain of SRY protein severely. Conclusions This study identified three novel mutations of SRY gene causing 46,XY DSD. The detection rate of SRY gene mutation was about 5%. For all the 46, XY DSD patients, it is recommended that SRY gene testing be performed to identify the etiology of the disease.

Key words: SRY gene, gonadal dysgenesis, disorder of sex development