| Title | Mutational analysis of the FAM175A gene in patients with premature ovarian insufficiency |
| Authors | Xu, Xiaofei Zhang, Yingxin Zhao, Shidou Bian, Yuehong Ning, Yunna Qin, Yingying |
| Affiliation | Shandong Univ, Ctr Reprod Med, Natl Res Ctr Assisted Reprod Technol & Reprod Gen, Key Lab Reprod Endocrinol,Minist Educ, Jinan, Shandong, Peoples R China Peking Univ, Ctr Reprod Med, Dept Obstet & Gynecol, Minist Educ,Key Lab Assisted Reprod,Hosp 3, Beijing, Peoples R China Chinese Univ Hong Kong, Dept Obstet & Gynecol, Hong Kong, Peoples R China |
| Keywords | DNA damage FAM175A Premature ovarian insufficiency Single-nucleotide polymorphism (SNP) |
| Issue Date | 2019 |
| Publisher | REPRODUCTIVE BIOMEDICINE ONLINE |
| Abstract | Research question: The family with sequence similarity 175 member A gene (FAM175A; also known as ABRAXAS1, CCDC98 and ABRA1), a member of the DNA repair family, contributes to the BRCA1 (BRCA1 DNA repair associated)dependent DNA damage response and is associated with age at natural menopause. However, it remains poorly understood whether sequence variants in FAM175A are causative for premature ovarian insufficiency (POI). The aim of this study was to investigate whether mutations in the gene FAM175A were present in patients with POI. Design: A total of 400 women with idiopathic POI and 498 control women with regular menstruation (306 age-matched women and 192 women over 40 years old) were recruited. After Sanger sequencing of FAM175A, functional experiments were carried out to explore the deleterious effects of the identified variation. DNA damage was subsequently induced by mitomycin C (MMC), and DNA repair capacity and G2-M checkpoint activation were evaluated by examining the phosphorylation level of H2AX (H2A histone family, member X) and the percentage of mitotic cells, respectively. Results: One rare single-nucleotide polymorphism, rs755187051 in gene FAM175A, c.C727G (p.L243V), was identified in two patients but absent in the 498 controls. The functional experiments demonstrated that overexpression of variant p.L243V in HeLa cells resulted in a similar sensitivity to MMC-induced damage compared with cells transfected with wild-type FAM175A. Moreover, after treatment with MMC, there were no differences in DNA repair capacity and G2-M checkpoint activation between the mutant and wild-type genes. Conclusion: Our results suggest that the p.L243V variant of FAM175A may not be causative for POI. The contribution of FAM175A to POI needs further exploration. |
| URI | http://hdl.handle.net/20.500.11897/548012 |
| ISSN | 1472-6483 |
| DOI | 10.1016/j.rbmo.2019.02.006 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 |
