Xiaopei Zhou1, Lixia Zhu2, Meiqi Hou1, Yanling Wu1, Zhou Li2, Jiarui Wang1, Zhenxing Liu1, Dazhi Zhang1, Lei Jin3, Xianqin Zhang4. 1. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China. 2. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. 3. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. Ljin@tjh.tjmu.edu.cn. 4. Key Laboratory of Molecular Biophysics of the Ministry of Education, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, 430074, Hubei, China. xqzhang04@hust.edu.cn.
Abstract
PURPOSE: To identify the disease-causing gene in a family with female infertility and fertilization failure. METHODS: Whole-exome sequencing and Sanger sequencing were used to identify the disease-causing gene in a female with infertility and fertilization failure. Subcellular localization and western blot analysis were used to check the effect of mutations. RESULTS: We identified novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female with infertility and fertilization failure. The p.Arg200Ter mutant WEE2 gene produce truncated protein and mainly located in the nucleus, the same as the wild protein, while the p.Trp440Ser mutant WEE2 proteins are located in the nucleus and cytoplasm and the expression level of p.Trp440Ser mutant WEE2 protein is reduced significantly compared with that of wild-type WEE2. CONCLUSIONS: We discovered novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female whose oocytes could not form pronucleus after intracytoplasmic sperm injection (ICSI). Moreover, mutations in WEE2 gene affect the normal function of WEE2 proteins and cause fertilization failure.
PURPOSE: To identify the disease-causing gene in a family with female infertility and fertilization failure. METHODS: Whole-exome sequencing and Sanger sequencing were used to identify the disease-causing gene in a female with infertility and fertilization failure. Subcellular localization and western blot analysis were used to check the effect of mutations. RESULTS: We identified novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female with infertility and fertilization failure. The p.Arg200Ter mutant WEE2 gene produce truncated protein and mainly located in the nucleus, the same as the wild protein, while the p.Trp440Ser mutant WEE2 proteins are located in the nucleus and cytoplasm and the expression level of p.Trp440Ser mutant WEE2 protein is reduced significantly compared with that of wild-type WEE2. CONCLUSIONS: We discovered novel compound heterozygous mutations c.598C>T (p.Arg200Ter) and c.1319G>C (p.Trp440Ser) in WEE2 gene in a female whose oocytes could not form pronucleus after intracytoplasmic sperm injection (ICSI). Moreover, mutations in WEE2 gene affect the normal function of WEE2 proteins and cause fertilization failure.
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