Molecular Genetic Studies Of Vaginal Oblique Syndrome

BackgroundOblique vaginal septum syndrome(OVSS)is a rare congenital malformation of the urogenital tract.It is also known as Herlyn-Werner-Wunderlich syndrome(HWWS)for foreign researchers.Anatomically it is characterised by a triad of didelphys uterus,obstructed hemivagina and ipsilateral renal agenesis.The specific pathogenesis is not clear yet.The most widely accepted hypothesis is that it results from mesonephric duct abnormalities resulting in abnormal fusion of mullerian duct,leading to agenesis or hypoplasia,defective vertical or lateral fusion,or resorption failure of paramesonephric ducts.Currently,only a small amount of sporadic cases has been reported.Thus it is difficult to analyze the genetic patterns of OVSS and study the etiology and molecular genetics mechanism.Materials and MethodsIn Peking Union Medical College,Beijing,China,we found one consanguineous Chinese Han pedigree affected by OVSS.The clinical data and peripheral blood DNA of the family members were collected.All the DNA samples were sequenced by whole-exome sequencing.After preliminary filtered,these suspected causative genes were cross-compared with the result of previous study,in which 20 sporadic OVSS cased were sequenced and analyzed.Common causative genes were verified by Sanger sequencing then.Results2 patients and 1 control of this pedigree were analyzed in this research.We obtained 167 candidate genes after whole-exome sequencing and pedigree analysis,and 25 genes were also highlighted by the previous study,according to its list of causative genes.After verification of Sanger sequencing,we finally get 2 candidate genes.ConclusionAccording to the results of whole-exome sequencing and bioinformatics analysis,the cases of OVSS in this family conformed to the sex-conditioned inheritance.The pathogenic genes may be ABCC2 and ADRA2B.Their functions need to be further investigated.