Fertility and sterility · 2015
Nonsense mutation of EMX2 is potential causative for uterus didelphysis: first molecular explanation for isolated incomplete müllerian fusion.
Клинический случайСтатьяПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Liu Shan, Gao Xuan, Qin Yingying, Liu Wen, Huang Tao, Ma Jinlong, Simpson Joe Leigh, Chen Zi-Jiang
Аннотация
OBJECTIVE: To investigate the association between human empty spiracles homeobox 2 gene (EMX2) and incomplete müllerian fusion (IMF).
DESIGN: Case-control study.
SETTING: 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.
DESIGN: Case-control study.
SETTING: 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.