Zhenxing Liu1, Lixia Zhu2, Jiarui Wang1, Geng Luo1, Qingsong Xi2, Xiaopei Zhou1, Zhou Li2, Xue Yang1, Jinliang Duan3, Lei Jin4, Xianqin Zhang5. 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 Medical Center, No. 924 Hospital of Chinese People's Liberation Army, Guilin, Guangxi, China. 4. Reproductive Medicine Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China. leijintongjih@qq.com. 5. 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 gene in 40 patients with female infertility due to oocyte maturation arrest. METHODS: Genomic DNA was extracted from peripheral blood of 40 patients and their family members. Whole-exome sequencing was performed on the patients, and the PATL2 mutations were identified and confirmed by Sanger sequencing. Harmfulness of the mutations was analyzed by SIFT, Polyphen-2, Mutation Taster, and M-CAP software, and we used western immunoblotting analysis to check the effect of mutations on PATL2 protein expression in vitro. RESULTS: Two novel missense mutations c.1528C>A (p.Pro510Thr) and c.1376C>A (p.Ser459Tyr) in PATL2 were identified in three patients (7.5%) from two consanguineous families in our cohort. We found that mutations in PATL2 resulted in variable oocyte phenotypes, including GV arrest, MI arrest, and morphologic abnormalities. Western immunoblotting analysis showed that the expression levels of the two novel mutant PATL2 proteins decreased significantly. CONCLUSIONS: We identified two novel PATL2 mutations that caused oocyte maturation arrest and abnormal morphology, and variable phenotypes in patients.
PURPOSE: To identify the disease gene in 40 patients with female infertility due to oocyte maturation arrest. METHODS: Genomic DNA was extracted from peripheral blood of 40 patients and their family members. Whole-exome sequencing was performed on the patients, and the PATL2 mutations were identified and confirmed by Sanger sequencing. Harmfulness of the mutations was analyzed by SIFT, Polyphen-2, Mutation Taster, and M-CAP software, and we used western immunoblotting analysis to check the effect of mutations on PATL2 protein expression in vitro. RESULTS: Two novel missense mutations c.1528C>A (p.Pro510Thr) and c.1376C>A (p.Ser459Tyr) in PATL2 were identified in three patients (7.5%) from two consanguineous families in our cohort. We found that mutations in PATL2 resulted in variable oocyte phenotypes, including GV arrest, MI arrest, and morphologic abnormalities. Western immunoblotting analysis showed that the expression levels of the two novel mutant PATL2 proteins decreased significantly. CONCLUSIONS: We identified two novel PATL2 mutations that caused oocyte maturation arrest and abnormal morphology, and variable phenotypes in patients.
Authors: Charles H Spruck; Maria P de Miguel; Adrian P L Smith; Aimee Ryan; Paula Stein; Richard M Schultz; A Jeannine Lincoln; Peter J Donovan; Steven I Reed Journal: Science Date: 2003-04-25 Impact factor: 47.728
Authors: Lena Wartosch; Karen Schindler; Melina Schuh; Jennifer R Gruhn; Eva R Hoffmann; Rajiv C McCoy; Jinchuan Xing Journal: Prenat Diagn Date: 2021-03-22 Impact factor: 3.050