Whole-exome sequencing reveals genetic variants in ERC1 and KCNG4 associated with complete hydatidiform mole in Chinese Han women

Yan Yu; Bingjian Lu; Weiguo Lu; Shuang Li; Xiuqin Li; Xinyu Wang; Xiaoyun Wan; Yaxia Chen; Suwen Feng; Yao Jia; Ru Yang; Fangxu Tang; Xiong Li; Shulan Zhang; Xinyan Wang; Heng Wei; Zhilan Peng; Lin Lu; Huizhen Zhong; Linjun Zhao; Zhangqian Huang; Lin Lin; Weihong Shen; Yan Lu; Zhu Cao; Jian Zou; Yuejiang Ma; Xiaojing Chen; Qifang Tian; Shiming Lu; Pengyuan Liu; Ding Ma; Xing Xie; Xiaodong Cheng

doi:10.18632/oncotarget.20769

Whole-exome sequencing reveals genetic variants in ERC1 and KCNG4 associated with complete hydatidiform mole in Chinese Han women

Oncotarget. 2017 Sep 8;8(43):75264-75271. doi: 10.18632/oncotarget.20769. eCollection 2017 Sep 26.

Authors

Yan Yu¹, Bingjian Lu², Weiguo Lu³, Shuang Li⁴, Xiuqin Li⁵, Xinyu Wang³, Xiaoyun Wan³, Yaxia Chen³, Suwen Feng³, Yao Jia⁴, Ru Yang⁴, Fangxu Tang⁴, Xiong Li⁴, Shulan Zhang⁵, Xinyan Wang⁵, Heng Wei⁵, Zhilan Peng⁶, Lin Lu⁶, Huizhen Zhong⁷, Linjun Zhao⁷, Zhangqian Huang⁸, Lin Lin⁹, Weihong Shen⁹, Yan Lu^{3

10}, Zhu Cao¹, Jian Zou¹, Yuejiang Ma¹, Xiaojing Chen¹, Qifang Tian³, Shiming Lu¹¹, Pengyuan Liu^{10

12}, Ding Ma⁴, Xing Xie³, Xiaodong Cheng³

Affiliations

¹ Key Laboratory of Women's Reproductive Health of Zhejiang Province, Women's Hospital School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
² Department of Surgical Pathology, Women's Hospital School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
³ Department of Gynecologic Oncology, Women's Hospital School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
⁴ Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
⁵ Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China.
⁶ Department of Obstetrics and Gynecology, West China Second Hospital of Sichuan University, Chengdu, Sichuan, China.
⁷ Department of Obstetrics and Gynecology, Ningbo Women and Children's Hospital, Ningbo, Zhejiang, China.
⁸ Department of Obstetrics and Gynecology, Shaoxing Women and Children Hospital, Shaoxing, Zhejiang, China.
⁹ Zhejiang University Hospital, Zhejiang University, Hangzhou, Zhejiang, China.
¹⁰ Institute for Translational Medicine School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
¹¹ Department of Clinical Laboratory, Women's Hospital School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
¹² Sir Run Run Shaw Hospital School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.

Abstract

Complete hydatidiform mole (CHM) is a rare pregnancy-related disease with invasive potential. The genetics underlying the sporadic form of CHM have not been addressed previously, but maternal genetic variants may be involved in biparental CHM. We performed whole-exome sequencing of 51 patients with CHM and 47 healthy women to identify genetic variants associated with CHM. In addition, candidate variants were analyzed using single base extension and Matrix Assisted Laser Desorption/Ionization-Time of Flight Mass Spectrometry in 199 CHM patients and 400 healthy controls. We validated candidate variants using Sanger sequencing in 250 cases and 652 controls, including 205 new controls. Two single nucleotide polymorphisms, c.G48C(p.Q16H) inERC1 and c.G1114A(p.G372S) in KCNG4, were associated with an increased risk of CHM (p<0.05). These variants may contribute to the pathogenesis of CHM and could be used to screen pregnant women for this genetic abnormality.

Keywords: complete hydatidiform mole; genomics; pathogenesis; whole-exome sequencing.