The Correlation Study On EMX2 Mutations And Müllerian Duct Anomalies In Women Of Hebei Area Of China

ABSTRACTObjective: The aim of this correlational study is to investigate the relevance between Müllerian duct anomalies of women of Hebei area of China and the mutations of EMX2 gene coding region, by extracting the whole genome from those women of Hebei area of China who have Müllerian duct anomalies and then screening the mutations of 3 exons and its corresponding flanking sequence of EMX2 gene.Methods: According to the American Society for Reproductive Medicine classification system standard, published by American Fertility Society(AFS), 97 Chinese females with Müllerian duct anomalies were recruited as experimental group, meanwhile, 110 Chinese females without Müllerian duct anomalies, who had ectopic pregnancy but used to be normal pregnant were recruited as control group. A variety of clinical manifestations can exist because of Müllerian duct anomalies. The experimental group included MRKH syndrome(congenital absence of the uterus and vagina, n=32), primordial uterus and absence of vagina(n=3), uterus didelphys with double cervix and complete longitudinal septum of vagina(n=1), uterus didelphys with double cervix/single cervix and not complete septum of vagina(n=4), uterus septus(complete or partial) complicated with longitudinal septum of vagina(n=12), uterus septus with no longitudinal septum(n=1), uterus bicornis(n=4), uterus unicornis complicated with rudimentary uterus or not(n=16), arcuate uterus(n=2), oblique vaginal septum syndrome(OVSS, characterized by uterus didelphys, double cervix, Oblique vaginal septum resulting in complete or partial vagina atresia and the ipsilateral renal agenesis)(n=6), atresia of the upper vagina with or without cervix aplasia and complicated with uterus of functional endometrium(n=3), transverse septum of vagina(n=2), and they were diagnosed by ultrasound, hysterosalpinography, hysteroscopy and laparoscopy. Those patients in experimental group or control group had a normal karyotype(46, XX) and normal female secondary sexual development. Separately extract the peripheral blood lymphocytes and whole genome DNA from the patients in experimental group and control group, and then amplify and sequence EMX2 gene including 3 exons and its corresponding flanking sequence by using polymerase chain reaction(PCR). Compare the results with the normal sequences in NCBI and analysis if the base is changing, missing or inserting in the 3 exons of EMX2 gene.Results:1 Compared with the normal sequences in NCBI, this experiment didn’t find any mutation of 3 exons and its corresponding flanking sequence of EMX2 gene, among 97 patients in experimental group and 110 patients in control group.2 The clinical data showed that 24 cases of experimental group had other system malformations(n=24/97, 24.74%) and 6 cases had more than one system abnormalities, consisting 6.19% of experimental group. They included congenital scoliosis(n=5/97, 5.15%), congenital vertebrate dysplasia(n=1/97, 1.03%), rachischisis(n=1/97, 1.03%) congenital rib deformities(n=4/97, 4.12%), congenital limb deformities/ polydactyly/ Oligodactyly(n=3/97, 3.09%), unilateral renal agenesis(n=12/97, 12.37%), ectopia kidney(n=2/97, 2.06%), congenital bladder orifice stricture(n=1/97, 1.03%), congenital heart disease(n=2/97, 2.06%) congenital imperforate anus(n=1/97, 1.03%), congenital Meckel’s diverticulum(n=1/97, 1.03%), congenital oblique inguinal hernia(n=2/97, 2.06%). The proportion of urethral system abnormalities, skeletal system malformations, cardiac malformations, digestive system abnormalities and other malformations of all the malformations was respectively 42.86%, 40.00%, 5.71%, 5.71%, 5.71% of 35 cases.Conclusions:1 The mutation of EMX2 gene coding region is not the common causes of Müllerian duct anomalies among women of Hebei area of China. We shoud learn more about the pathogenesis because of the limited cases.2 The Müllerian duct anomalies patients are always complicated with other system abnormalities.