Lingli Huang1,2, Yu Wang3, Fangting Lu4, Qi Jin4, Gaojie Song5, Jingjuan Ji4, Lihua Luo4, Rentao Jin6, Xianhong Tong7. 1. Center for Reproductive Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China. huangll163@163.com. 2. Department of Obstetrics and Gynecology, Anhui Provincial Hospital Affiliated to Anhui Medical University, Hefei, 230001, China. huangll163@163.com. 3. Reproductive Medicine Center, Department of Obstetrics and Gynecology, The First Affiliated Hospital of Anhui Medical University, Hefei, 230022, China. 4. Center for Reproductive Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China. 5. Shanghai Key Laboratory of Regulatory, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, 200241, China. 6. Center for Reproductive Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China. jrtao2001@163.com. 7. Center for Reproductive Medicine, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230001, Anhui, China. tong68xianhong@163.com.
Abstract
PURPOSE: This study aims to identify the genetic causes of 12 women with primary infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. METHODS: Genomic DNA was isolated from peripheral blood samples. Whole-exome sequencing was performed on the probands, and the identified variants were confirmed by Sanger sequencing. The pathogenicity of the identified variants on the protein was accessed in silico. And we used qRT-PCR to detect the possible effects of the novel mutation on the mRNA level of NLRP5. RESULTS: A novel homozygous frameshift variant (p.V429Efs*30) in NLRP5 and compound heterozygous variants with a novel frameshift variant (p.A297Efs*20) and a recurrent variant (c. 223-14_223-2delCCCTCCTGTTCCA) in PATL2 were identified in two unrelated affected individuals. qRT-PCR showed an obvious decrease of the mutant NLRP5 mRNA. In addition, the truncated proteins of NLRP5 and PATL2 were predicted to be non-functional due to the deletion of the most or the whole region of the critical functional domain(s) respectively. CONCLUSIONS: This study identified novel mutations in NLRP5 and PATL2, further expanding the mutational and phenotypic spectrum of both genes. This is the first report of the NLRP5 mutations that associates with oocyte maturation abnormality in humans.
PURPOSE: This study aims to identify the genetic causes of 12 women with primary infertility characterized by primarily oocyte maturation abnormality and consequent early embryonic arrest. METHODS: Genomic DNA was isolated from peripheral blood samples. Whole-exome sequencing was performed on the probands, and the identified variants were confirmed by Sanger sequencing. The pathogenicity of the identified variants on the protein was accessed in silico. And we used qRT-PCR to detect the possible effects of the novel mutation on the mRNA level of NLRP5. RESULTS: A novel homozygous frameshift variant (p.V429Efs*30) in NLRP5 and compound heterozygous variants with a novel frameshift variant (p.A297Efs*20) and a recurrent variant (c. 223-14_223-2delCCCTCCTGTTCCA) in PATL2 were identified in two unrelated affected individuals. qRT-PCR showed an obvious decrease of the mutant NLRP5 mRNA. In addition, the truncated proteins of NLRP5 and PATL2 were predicted to be non-functional due to the deletion of the most or the whole region of the critical functional domain(s) respectively. CONCLUSIONS: This study identified novel mutations in NLRP5 and PATL2, further expanding the mutational and phenotypic spectrum of both genes. This is the first report of the NLRP5 mutations that associates with oocyte maturation abnormality in humans.
Authors: Joshua T Mendell; Neda A Sharifi; Jennifer L Meyers; Francisco Martinez-Murillo; Harry C Dietz Journal: Nat Genet Date: 2004-09-26 Impact factor: 38.330
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: Louise E Docherty; Faisal I Rezwan; Rebecca L Poole; Claire L S Turner; Emma Kivuva; Eamonn R Maher; Sarah F Smithson; Julian P Hamilton-Shield; Michal Patalan; Maria Gizewska; Jaroslaw Peregud-Pogorzelski; Jasmin Beygo; Karin Buiting; Bernhard Horsthemke; Lukas Soellner; Matthias Begemann; Thomas Eggermann; Emma Baple; Sahar Mansour; I Karen Temple; Deborah J G Mackay Journal: Nat Commun Date: 2015-09-01 Impact factor: 14.919