Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, People's Republic of China; Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Beijing Chao-Yang Hospital Affiliated to Capital Medical University, Beijing, People's Republic of China.
Center for Reproductive Medicine, Provincial Hospital Affiliated to Shandong University, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Key Laboratory for Reproductive Endocrinology of Ministry of Education, Shandong Provincial Key Laboratory of Reproductive Medicine, Jinan, People's Republic of China.
Fertil Steril. 2015 Mar;103(3):769-74.e2. doi: 10.1016/j.fertnstert.2014.11.030. Epub 2015 Jan 7.
To investigate the association between human empty spiracles homeobox 2 gene (EMX2) and incomplete müllerian fusion (IMF).
Case-control study.
University-based hospital.
PATIENT(S): Cohort of 517 clinically well-characterized IMF cases and 563 control women.
INTERVENTION(S): None.
MAIN OUTCOME MEASURE(S): In cases and control women, direct sequencing of EMX2 exons and further functional studies; for functional studies, wild-type and mutant EMX2 expression plasmids constructed; human embryonic kidney cells (HEK293FT) transfected with empty vector, wild-type EMX2, mutant EMX2, and 1:1 combination (wild-type/mutant plasmids) with additional functional studies performed to clarify the deleterious effect of the novel mutation detected.
RESULT(S): A novel nonsense mutation p.E142X was detected in one woman with a didelphic uterus (1 of 517, 0.19%). The results of Western blot analysis confirmed that the mutation caused a truncated protein as predicted, and functional studies proved that it resulted in a dominant negative effect.
CONCLUSION(S): The novel nonsense mutation we detected-EMX2, p.E142X- resulted in a dominant negative effect. The functional data were exemplified in HEK293FT cells. This reinforced the likelihood that EMX2 contributed to the pathophysiology of IMF. Although it is uncommon (0.19%), EMX2 is the first gene identified that if perturbed may cause isolated IMF.
探讨人类空泡器官同源盒 2 基因（EMX2）与不完全苗勒管融合（IMF）之间的关联。
病例对照研究。
大学附属医院。
517 例临床特征明确的 IMF 病例和 563 例对照女性组成的队列。
无。
在病例和对照女性中，EMX2 外显子的直接测序和进一步的功能研究；对于功能研究，构建野生型和突变型 EMX2 表达质粒；用空载体、野生型 EMX2、突变型 EMX2 转染人胚肾细胞（HEK293FT），并进行额外的功能研究，以阐明检测到的新突变的有害影响。
在 1 例双子宫的女性中发现了 1 个新的无义突变 p.E142X（517 例中的 1 例，0.19%）。Western blot 分析的结果证实，该突变导致了预期的截短蛋白，功能研究证明其导致了显性负效应。
我们检测到的新无义突变-EMX2，p.E142X-导致了显性负效应。功能数据在 HEK293FT 细胞中得到了例证。这强化了 EMX2 可能导致 IMF 病理生理学的可能性。虽然罕见（0.19%），但 EMX2 是第一个被确定的基因，如果受到干扰，可能导致孤立的 IMF。
