In-Frame Variants in STAG3 Gene Cause Premature Ovarian Insufficiency
Premature ovarian insufficiency (POI) is a severe clinical syndrome defined by ovarian dysfunction in women less than 40 years old who generally manifest with infertility, menstrual disturbance, elevated gonadotrophins, and low estradiol levels. STAG3 is considered a genetic aetiology of POI, which...
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Frontiers Media S.A.
2019-11-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fgene.2019.01016/full |
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| author | Wen-Juan Xiao Wen-Bin He Wen-Bin He Wen-Bin He Ya-Xin Zhang Lan-Lan Meng Lan-Lan Meng Guang-Xiu Lu Guang-Xiu Lu Guang-Xiu Lu Ge Lin Ge Lin Ge Lin Yue-Qiu Tan Yue-Qiu Tan Yue-Qiu Tan Juan Du Juan Du Juan Du |
| author_facet | Wen-Juan Xiao Wen-Bin He Wen-Bin He Wen-Bin He Ya-Xin Zhang Lan-Lan Meng Lan-Lan Meng Guang-Xiu Lu Guang-Xiu Lu Guang-Xiu Lu Ge Lin Ge Lin Ge Lin Yue-Qiu Tan Yue-Qiu Tan Yue-Qiu Tan Juan Du Juan Du Juan Du |
| author_sort | Wen-Juan Xiao |
| collection | DOAJ |
| description | Premature ovarian insufficiency (POI) is a severe clinical syndrome defined by ovarian dysfunction in women less than 40 years old who generally manifest with infertility, menstrual disturbance, elevated gonadotrophins, and low estradiol levels. STAG3 is considered a genetic aetiology of POI, which facilitates entry of REC8 into the nucleus of a cell and plays an essential role in gametogenesis. At present, only six truncated variants associated with POI have been reported; there have been no reports of an in-frame variant of STAG3 causing POI. In this study, two novel homozygous in-frame variants (c.877_885del, p.293_295del; c.891_893dupTGA, p.297_298insAsp) in STAG3 were identified in two sisters with POI from a five-generation consanguineous Han Chinese family. To evaluate the effects of these two variants, we performed fluorescence localization and co-immunoprecipitation analyses using in vitro cell model. The two variants were shown to be pathogenic, as neither STAG3 nor REC8 entered nuclei, and interactions between mutant STAG3 and REC8 or SMC1A were absent. To the best of our knowledge, this is the first report on in-frame variants of STAG3 that cause POI. This finding extends the spectrum of variants in STAG3 and sheds new light on the genetic origins of POI. |
| first_indexed | 2024-12-14T02:40:11Z |
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| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-12-14T02:40:11Z |
| publishDate | 2019-11-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-14666d3c2a36409eaa4a77e8f40e36902022-12-21T23:20:02ZengFrontiers Media S.A.Frontiers in Genetics1664-80212019-11-011010.3389/fgene.2019.01016466471In-Frame Variants in STAG3 Gene Cause Premature Ovarian InsufficiencyWen-Juan Xiao0Wen-Bin He1Wen-Bin He2Wen-Bin He3Ya-Xin Zhang4Lan-Lan Meng5Lan-Lan Meng6Guang-Xiu Lu7Guang-Xiu Lu8Guang-Xiu Lu9Ge Lin10Ge Lin11Ge Lin12Yue-Qiu Tan13Yue-Qiu Tan14Yue-Qiu Tan15Juan Du16Juan Du17Juan Du18Institute of Reproduction and Stem Cell Engineering, Central South University, Changsha, ChinaInstitute of Reproduction and Stem Cell Engineering, Central South University, Changsha, ChinaGenetic Center, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, ChinaNHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, ChinaInstitute of Reproduction and Stem Cell Engineering, Central South University, Changsha, ChinaGenetic Center, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, ChinaNHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, ChinaInstitute of Reproduction and Stem Cell Engineering, Central South University, Changsha, ChinaGenetic Center, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, ChinaNHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, ChinaInstitute of Reproduction and Stem Cell Engineering, Central South University, Changsha, ChinaGenetic Center, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, ChinaNHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, ChinaInstitute of Reproduction and Stem Cell Engineering, Central South University, Changsha, ChinaGenetic Center, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, ChinaNHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, ChinaInstitute of Reproduction and Stem Cell Engineering, Central South University, Changsha, ChinaGenetic Center, Reproductive and Genetic Hospital of CITIC-Xiangya, Changsha, ChinaNHC Key Laboratory of Human Stem Cell and Reproductive Engineering, Central South University, Changsha, ChinaPremature ovarian insufficiency (POI) is a severe clinical syndrome defined by ovarian dysfunction in women less than 40 years old who generally manifest with infertility, menstrual disturbance, elevated gonadotrophins, and low estradiol levels. STAG3 is considered a genetic aetiology of POI, which facilitates entry of REC8 into the nucleus of a cell and plays an essential role in gametogenesis. At present, only six truncated variants associated with POI have been reported; there have been no reports of an in-frame variant of STAG3 causing POI. In this study, two novel homozygous in-frame variants (c.877_885del, p.293_295del; c.891_893dupTGA, p.297_298insAsp) in STAG3 were identified in two sisters with POI from a five-generation consanguineous Han Chinese family. To evaluate the effects of these two variants, we performed fluorescence localization and co-immunoprecipitation analyses using in vitro cell model. The two variants were shown to be pathogenic, as neither STAG3 nor REC8 entered nuclei, and interactions between mutant STAG3 and REC8 or SMC1A were absent. To the best of our knowledge, this is the first report on in-frame variants of STAG3 that cause POI. This finding extends the spectrum of variants in STAG3 and sheds new light on the genetic origins of POI.https://www.frontiersin.org/article/10.3389/fgene.2019.01016/fullpremature ovarian insufficiencySTAG3 genein-frame variantfluorescence localizationco-immunoprecipitation |
| spellingShingle | Wen-Juan Xiao Wen-Bin He Wen-Bin He Wen-Bin He Ya-Xin Zhang Lan-Lan Meng Lan-Lan Meng Guang-Xiu Lu Guang-Xiu Lu Guang-Xiu Lu Ge Lin Ge Lin Ge Lin Yue-Qiu Tan Yue-Qiu Tan Yue-Qiu Tan Juan Du Juan Du Juan Du In-Frame Variants in STAG3 Gene Cause Premature Ovarian Insufficiency Frontiers in Genetics premature ovarian insufficiency STAG3 gene in-frame variant fluorescence localization co-immunoprecipitation |
| title | In-Frame Variants in STAG3 Gene Cause Premature Ovarian Insufficiency |
| title_full | In-Frame Variants in STAG3 Gene Cause Premature Ovarian Insufficiency |
| title_fullStr | In-Frame Variants in STAG3 Gene Cause Premature Ovarian Insufficiency |
| title_full_unstemmed | In-Frame Variants in STAG3 Gene Cause Premature Ovarian Insufficiency |
| title_short | In-Frame Variants in STAG3 Gene Cause Premature Ovarian Insufficiency |
| title_sort | in frame variants in stag3 gene cause premature ovarian insufficiency |
| topic | premature ovarian insufficiency STAG3 gene in-frame variant fluorescence localization co-immunoprecipitation |
| url | https://www.frontiersin.org/article/10.3389/fgene.2019.01016/full |
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