Molecular Genetics And Clinical Studies Of Oblique Vaginal Septum Syndrome

Background Herlyn-Werner-Wunderlich syndrome(HWWS)is a rare congenital malformation,which mainly manifests as uterine didelphys,obstructed hemivagina and usually combined with ipsilateral renal anomaly.Due to the small amounts of cases and few familial clustering,it is very difficult to explore the mode of inheritance and genetic etiology of HWWS.So far,there have been few studies with positive conclusions of causative genes of HWWS.Methods The first part of this study,13 trio families(probands and her biological parents)and 50 patients diagnosed with HWWS were collected.All patients' blood samples were collected for whole genome sequencing and following bioinformatics analysis.According to the analysis results,the causative genes were screened out.The mutation load of the suspected causative genes was analyzed in healthy people cohort,and the mutations of the suspected causative genes were verified in the sequencing results of the existing female paramesonephric duct malformations cohort.Results All sequencing data of 13 trio families and 50 patients were qualified and included in bioinformatics analysis.Among them,3 patients with HWWS carried a frameshift mutation of ZNF662,2 cases of PZP gene mutation,and 1 case of FAM83B,WNT8A,TBX6 gene mutation each.The mutation frequencies of ZNF662,PZP,FAM83B,and WNT8A are significantly different from those of healthy women.In the female paramesonephric duct malformations cohort,3 patients with MRKH syndrome were found to carry ZNF662,PZP,and TBX6 frameshift mutations,1 patient with MRKH syndrome and 1 patient with vaginal atresia carried PZP and TBX6 stop-gained mutations,respectively.Conclusions ZNF662,PZP,FAM83B,WNT8A,TBX6 are suspected causative genes for HWWS.Background Herlyn-Werner,Wunderlich syndrome(HWWS)is a rare disease,which is usually divided into three types." Classification ? "HWWS is a new type.The phenotype of patients with"classification ?" HWWS is similar to that of patients with rudimentary uterine horn.These two types of patients cannot be clearly differentiated only by clinical features and ultrasound examinations.Methods In the second part of this study,patients diagnosed with "classification ?" HWWS and rudimentary uterine horn at Department of Obstetrics and Gynecology,PUMCH,Beijing,China from January 2018 to April 2021 were collected.The clinical data were all collected.Patients with "classification ?" HWWS or rudimentary uterine horn were clearly diagnosed after the operation.Compare the similarities and differences between these two types of patients in terms of ultrasound manifestations,combined malformations,and comorbidities,in order to provide a reference for clinical differentiation.Results There is no significant difference in treating age between patients with "classification ?"HWWS and rudimentary uterine horn.The most common clinical manifestations are dysmenorrhea.Ultrasonography showed that rudimentary uterine horn was smaller than unicornuate uterus,and there was no significant difference in the size of the uterus on both sides of septum in "classification ?" HWWS.Patients with "classification ?" HWWS are more likely to have unilateral renal agenesis and endometriosis.Conclusions There are significant differences in the volume of uterus and the incidence of unilateral renal agenesis and endometriosis in patients with "classification ?" HWWS and rudimentary uterine horn.