Ruyi Liu1, Yifan Zhou2, Qiaoli Li1, Biaobang Chen3, Zhou Zhou1, Lan Wang2, Lei Wang1, Qing Sang4, Lei Jin5. 1. Institute of Pediatrics, Children's Hospital of Fudan University, the Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China. 2. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. 3. NHC Key Lab of Reproduction Regulation (Shanghai Institute for Biomedical and Pharmaceutical Technologies), Fudan University, Shanghai, 200032, China. 4. Institute of Pediatrics, Children's Hospital of Fudan University, the Institutes of Biomedical Sciences, and the State Key Laboratory of Genetic Engineering, Fudan University, Shanghai, 200032, China. sangqing@fudan.edu.cn. 5. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China. ljin@tjh.tjmu.edu.cn.
Abstract
PURPOSE: "Zygotic cleavage failure" is an embryonic phenotype that causes female infertility and failure of in vitro fertilization and/or intracytoplasmic sperm injection. We aimed to identify pathogenic variants in a female infertility patient from a consanguineous family with the "zygotic cleavage failure" phenotype. METHODS: Whole-exome sequencing was performed in the affected patient; Sanger sequencing was used to confirm the identified variant. The functional effect of the identified variant was further investigated in HeLa cells. RESULTS: We identified a novel homozygous missense mutation in BTG4 (c.285G > C, p.W95C) in the affected individual. Co-immunoprecipitation in HeLa cells showed the complete loss of the interaction between the p.W95C BTG4 variant protein and CNOT7. CONCLUSION: This study confirms our previous research and expands the mutational spectrum of BTG4. Our findings complement the diagnostic genetic basis for "zygotic cleavage failure" patients and suggest that BTG4 may be a good target for future therapeutic strategies.
PURPOSE: "Zygotic cleavage failure" is an embryonic phenotype that causes female infertility and failure of in vitro fertilization and/or intracytoplasmic sperm injection. We aimed to identify pathogenic variants in a female infertility patient from a consanguineous family with the "zygotic cleavage failure" phenotype. METHODS: Whole-exome sequencing was performed in the affected patient; Sanger sequencing was used to confirm the identified variant. The functional effect of the identified variant was further investigated in HeLa cells. RESULTS: We identified a novel homozygous missense mutation in BTG4 (c.285G > C, p.W95C) in the affected individual. Co-immunoprecipitation in HeLa cells showed the complete loss of the interaction between the p.W95C BTG4 variant protein and CNOT7. CONCLUSION: This study confirms our previous research and expands the mutational spectrum of BTG4. Our findings complement the diagnostic genetic basis for "zygotic cleavage failure" patients and suggest that BTG4 may be a good target for future therapeutic strategies.
Authors: Yao Xu; Yingli Shi; Jing Fu; Min Yu; Ruizhi Feng; Qing Sang; Bo Liang; Biaobang Chen; Ronggui Qu; Bin Li; Zheng Yan; Xiaoyan Mao; Yanping Kuang; Li Jin; Lin He; Xiaoxi Sun; Lei Wang Journal: Am J Hum Genet Date: 2016-08-18 Impact factor: 11.025
Authors: Anas M Alazami; Salma M Awad; Serdar Coskun; Saad Al-Hassan; Hadia Hijazi; Firdous M Abdulwahab; Coralie Poizat; Fowzan S Alkuraya Journal: Genome Biol Date: 2015-11-05 Impact factor: 13.583