Pathogenic Variations of Homologous Recombination Gene HSF2BP Identified in Sporadic Patients With Premature Ovarian Insufficiency

Shan Li; Weiwei Xu; Bingying Xu; Shuchang Gao; Qian Zhang; Yingying Qin; Ting Guo

doi:10.3389/fcell.2021.768123

Pathogenic Variations of Homologous Recombination Gene HSF2BP Identified in Sporadic Patients With Premature Ovarian Insufficiency

Front Cell Dev Biol. 2022 Jan 31:9:768123. doi: 10.3389/fcell.2021.768123. eCollection 2021.

Authors

Shan Li^{1

2

3

4

5}, Weiwei Xu^{1

2

3

4

5}, Bingying Xu^{1

2

3

4

5}, Shuchang Gao^{1

2

3

4

5}, Qian Zhang^{1

2

3

4

5}, Yingying Qin^{1

2

3

4

5}, Ting Guo^{1

2

3

4

5}

Affiliations

¹ Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, China.
² National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan, China.
³ Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, China.
⁴ Shandong Provincial Clinical Medicine Research Center for Reproductive Health, Shandong University, Jinan, China.
⁵ Reproductive Hospital Affiliated to Shandong University, Jinan, China.

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: HSF2BP; gene mutation; homologous recombination; premature ovarian insufficiency; whole-exome sequencing.