Nonsense mutation of EMX2 is potential causative for uterus didelphysis First molecular explanation for isolated incomplete müllerian fusion

We identified a novel nonsense mutation p.E142X in EMX2, resulting in truncated protein with a dominant negative effect. It reinforced the likelihood that EMX2 contributed to the pathophysiology of IMF.

Shan Liu, M.D., Ph.D., Xuan Gao, M.D., Yingying Qin, M.D., Ph.D., Wen Liu, M.S., Tao Huang, M.S., Jinlong Ma, M.D., Ph.D., Joe Leigh Simpson, M.D., Ph.D., Zi-Jiang Chen, M.D., Ph.D.

Volume 103, Issue 3, Pages 769-774


To investigate the association between human empty spiracles homeobox 2 gene (EMX2) and incomplete müllerian fusion (IMF).

Case-control study.

University-based hospital.

Cohort of 517 clinically well-characterized IMF cases and 563 control women.


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.

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.

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.

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