Mutations In Wnt4Are Not Responsible For Mullerian Duct Abnormalities In Chinese Women

BACKGRAOUNDS Mullerian duct abnormalities (MDAs), presenting to women suffering congenital absence or severe hyperplasia of the female genital tract, due to embryonic mullerian dysplasias and mullerian improper fusion, including congenital vagina and uterus defect [Mayer-Rokitansky-Kuster-Hauser (MRKHs) syndrome], unicornuate uterus, didelphic uterus, bicornuate uterus, septate uterus, and vaginal septum, and these malformations can be observered in about5%of infertile women and25%of early miscarriage. Mullerian abnormalities frequently overlaps with other various syndromes or associations especially renal, vertebral, hearing, more rarely, cardiac and digital anomalies. The genetic factor was thought to be the major causes, in addition to some foregone known etiology, such as exposure to thalidomide-like teratogens or radioactive material. WNT4gene located at Ip35and encodes secreted signaling protein. The WNT4protein may function as a transcriptional factor and plays a crucial role in sexual differentiation, nephrogenesis and female genital tract development. Wnt4-null female mice presented with sex reversal, high androgen level, renal aberration, adrenal dysfunction and poor ovarian reserve. Previous reports showed that WNT4mutations resulted in resembling MRKH syndrome with androgen excess. The current study is the first to investigate mutation of WNT4in a larger cohort.OBJECTIVES To investigate whether or not the coding region of the WNT4gene mutation existed in Chinese Han women with idiopathtic MDAs.METHODS A cohort of189clinically well-characterized Chinese Han females with MDAs were recruited from, including MRKH syndrome (n=10), uterine agenesis (n=5), uterus didelphys (n=37), septate uterus (n=40), bicornuate uterus (n=43) and unicornuate uterus (n=54). One hundred and ninety eight females, who asked for infertility treatment because of tubal factor or male factor were included as controls. Five exons of WNT4gene were sequenced in all cases and controls. The objective fragments were amplified by PCR before sequenced, then compared with the HanMap project in NCBI.RESULTS One known SNPs in exon2(rs16826648) and one novel synonymous variation in exon5(c.1091G>A) were found, the latter of which was absent in all198controls. The patient carrying the mutation c.1091G>A was diagnosed with unicornuate uterus, but without any other somatic malformation.CONCLUSIONS:Mutations in the coding region of WNT4are not responsible for MDAs in Chinese. More studies are needed to elucidate the genetic etiology of MDAs in Chinese Han women.