Lin Zhao1, Yichun Guan2, Wenjing Wang1, Biaobang Chen3, Shiru Xu4, Ling Wu5, Zheng Yan5, Bin Li5, Jing Fu6, Rong Shi7, Juanzi Shi7, Jing Du3, Qiaoli Li1, Zhihua Zhang1, Jian Mu1, Zhou Zhou1, Jie Dong1, Li Jin1, Lin He8, Xiaoxi Sun6, Yanping Kuang5, Lei Wang9,10,11, Qing Sang12,13. 1. Institute of Pediatrics, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China. 2. Department of Reproductive Medicine, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China. 3. NHC Key Lab of Reproduction Regulation (Shanghai Institute of Planned Parenthood Research), Fudan University, Shanghai, China. 4. Fertility Center, Shenzhen Zhongshan Urology Hospital, Shenzhen, Guangdong, China. 5. Reproductive Medicine Center, Shanghai Ninth Hospital, Shanghai Jiao Tong University, Shanghai, China. 6. Shanghai Ji Ai Genetics and IVF Institute, Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China. 7. Reproductive Medicine Center, Shaanxi Maternal and Child Care Service Center, Shaanxi, China. 8. Bio-X Center, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders, Ministry of Education, Shanghai Jiao Tong University, Shanghai, China. 9. Institute of Pediatrics, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China. wangleiwanglei@fudan.edu.cn. 10. Zhuhai Fudan Innovation Institute, Zhuhai, Guangdong, China. wangleiwanglei@fudan.edu.cn. 11. Shanghai Center for Women and Children's Health, Shanghai, China. wangleiwanglei@fudan.edu.cn. 12. Institute of Pediatrics, Children's Hospital of Fudan University and the Shanghai Key Laboratory of Medical Epigenetics, the International Co-laboratory of Medical Epigenetics and Metabolism, Ministry of Science and Technology and Institutes of Biomedical Sciences, State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China. sangqing@fudan.edu.cn. 13. Zhuhai Fudan Innovation Institute, Zhuhai, Guangdong, China. sangqing@fudan.edu.cn.
Abstract
PURPOSE: We aimed to identify novel variants in TUBB8 and corresponding new abnormal phenotypes in oocytes/fertilization/ embryonic development responsible for female infertility. METHODS: Sanger sequencing of TUBB8 was performed in infertile women with abnormalities in oocyte maturation or embryonic development. The effects of the variants were evaluated in patients' oocytes by morphological observations and immunofluorescence. RESULTS: We identified 34 novel variants of TUBB8 in 51 patients who were diagnosed with abnormalities in oocyte maturation or early embryonic development. We found a novel phenotype in which large polar bodies were present in three independent patients possibly associated with a recurrent variant. Moreover, we identified a novel type of TUBB8 variant consisting of an in-frame deletion-insertion, which has not been previously reported. CONCLUSIONS: Our present study identified 34 novel variants in TUBB8 in 51 patients. These patients show oocyte maturation arrest, oocytes with large polar body, fertilization failure, early embryonic arrest or embryonic implantation failure. These results expand the kinds of variants and phenotypic spectrum of TUBB8 variants with regard to female infertility.
PURPOSE: We aimed to identify novel variants in TUBB8 and corresponding new abnormal phenotypes in oocytes/fertilization/ embryonic development responsible for female infertility. METHODS: Sanger sequencing of TUBB8 was performed in infertile women with abnormalities in oocyte maturation or embryonic development. The effects of the variants were evaluated in patients' oocytes by morphological observations and immunofluorescence. RESULTS: We identified 34 novel variants of TUBB8 in 51 patients who were diagnosed with abnormalities in oocyte maturation or early embryonic development. We found a novel phenotype in which large polar bodies were present in three independent patients possibly associated with a recurrent variant. Moreover, we identified a novel type of TUBB8 variant consisting of an in-frame deletion-insertion, which has not been previously reported. CONCLUSIONS: Our present study identified 34 novel variants in TUBB8 in 51 patients. These patients show oocyte maturation arrest, oocytes with large polar body, fertilization failure, early embryonic arrest or embryonic implantation failure. These results expand the kinds of variants and phenotypic spectrum of TUBB8 variants with regard to female infertility.
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