Frontiers in Cell and Developmental Biology (Jan 2022)
Pathogenic Variations of Homologous Recombination Gene HSF2BP Identified in Sporadic Patients With Premature Ovarian Insufficiency
- Shan Li,
- Shan Li,
- Shan Li,
- Shan Li,
- Shan Li,
- Weiwei Xu,
- Weiwei Xu,
- Weiwei Xu,
- Weiwei Xu,
- Weiwei Xu,
- Bingying Xu,
- Bingying Xu,
- Bingying Xu,
- Bingying Xu,
- Bingying Xu,
- Shuchang Gao,
- Shuchang Gao,
- Shuchang Gao,
- Shuchang Gao,
- Shuchang Gao,
- Qian Zhang,
- Qian Zhang,
- Qian Zhang,
- Qian Zhang,
- Qian Zhang,
- Yingying Qin,
- Yingying Qin,
- Yingying Qin,
- Yingying Qin,
- Yingying Qin,
- Ting Guo,
- Ting Guo,
- Ting Guo,
- Ting Guo,
- Ting Guo
Affiliations
- Shan Li
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shan Li
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Shan Li
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Shan Li
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
- Shan Li
- Reproductive Hospital Affiliated to Shandong University, Jinan, China
- Weiwei Xu
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Weiwei Xu
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Weiwei Xu
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Weiwei Xu
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
- Weiwei Xu
- Reproductive Hospital Affiliated to Shandong University, Jinan, China
- Bingying Xu
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Bingying Xu
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Bingying Xu
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Bingying Xu
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
- Bingying Xu
- Reproductive Hospital Affiliated to Shandong University, Jinan, China
- Shuchang Gao
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Shuchang Gao
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Shuchang Gao
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Shuchang Gao
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
- Shuchang Gao
- Reproductive Hospital Affiliated to Shandong University, Jinan, China
- Qian Zhang
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Qian Zhang
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Qian Zhang
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Qian Zhang
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
- Qian Zhang
- Reproductive Hospital Affiliated to Shandong University, Jinan, China
- Yingying Qin
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Yingying Qin
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Yingying Qin
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Yingying Qin
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
- Yingying Qin
- Reproductive Hospital Affiliated to Shandong University, Jinan, China
- Ting Guo
- Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China
- Ting Guo
- National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China
- Ting Guo
- Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China
- Ting Guo
- Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China
- Ting Guo
- Reproductive Hospital Affiliated to Shandong University, Jinan, China
- DOI
- https://doi.org/10.3389/fcell.2021.768123
- Journal volume & issue
-
Vol. 9
Abstract
Premature ovarian insufficiency (POI) is defined as depletion of ovarian function before 40 years of age, which affects 3.7% of women in reproductive age. The etiology of POI is heterogeneous. Recently, with the widespread use of whole-exome sequencing (WES), the DNA repair genes, especially for those involved in meiosis progress, were enriched in the causative gene spectrum of POI. In this study, through the largest in-house WES database of 1,030 patients with sporadic POI, we identified two novel homozygous variations in HSF2BP (c.382T>C, p.C128R; c.557T>C, p.L186P). An in vitro functional study revealed that both variations impaired the nuclear location of HSF2BP and affected its DNA repair capacity. Our studies highlighted the essential role of meiotic homologous recombination genes in the pathogenesis of sporadic POI.
Keywords
- premature ovarian insufficiency
- homologous recombination
- HSF2BP
- whole-exome sequencing
- gene mutation
