Clinical Research On Complete Gonadal Dysgenesis With Gonadal Neoplasia Caused By SRY Gene Mutation

Objective: The mutations in SRY gene and other genes associated with sex development can result in 46,XY complete gonadal dysgenesis(46,XY CGD),always accompanied with a high risk of gonadal neoplasia.With analyzing a case report and the meta-analysis of literature being searched,this paper intends to find out the pathogenic genes and tumor risk of 46,XY CGD,which could provide help for the diagnosis and treatment of 46,XY CGD.Methods: A 13-year-7-month old girl,due to lack of secondary sexual characteristics and growth retardation,was admitted to the Department of Pediatrics of the First Hospital of Zhejiang University in 2018.The patient was 142.4 cm tall(-2.6SDS)and weighed 33.5 kg.She was in Tanner I stage and had no pubic hair.The karyotype was 46,XY.The reproductive hormones,ultrasonography and gonadectomy were performed.Gene testing was made by trio-WES and confirmed by Sanger sequencing.And according to the keywords "disorder of sex development","tumor","46,XY CGD" and "SRY",Pub Med,CNKI,Web of Science and MEDLINE databases were searched to collect the cases caused by SRY gene mutations up to April in 2018.Results: The patient lacked secondary sexual characteristics with short stature and female external genitalia.Reproductive hormones showed LH44.8m IU/m L,FSH124.6m IU/m L,E2<11.8pg/ml,T36.0ng/ml,ACTH,cortisol and 17-hydroxyprogesterone were normal.The primordial uterus and streak gonads were visualized by ultrasound and gonadectomy.Bilateral gonadoblastoma coexisting with dysgerminoma were histopathologically diagnosed.Trio-WES revealed a new mutation in the SRY gene(c.36 dup C,p.N13Qfs2)which located at the upstream of the HMG box.With searching those databases,there were 55 cases of 46,XY CGD caused by mutated SRY gene being collected,and mutations located at the HMG box accounted for 76.4%.The incidence of tumor,gonadoblastoma and dysgerminoma was 43.6%,34.5% and 14.5%,respectively.Conclusions: The proband was diagnosed as 46,XY CGD with gonadal neoplasia caused by a new mutation(c.36 dup C,p.N13Qfs2)in the SRY gene.This frameshift mutation was rare and located at the upstream of the HMG box.46,XY CGD patients caused by mutated SRY gene have a high risk of gonadal neoplasia.The most common tumor was gonadoblastoma,followed by dysgerminoma.