Wei Zheng1, Longbin Chen2,3, Jing Dai2,3, Can Dai1, Jing Guo1, Changfu Lu1,2,3, Fei Gong1,2,3, Guangxiu Lu1,2,3, Ge Lin4,5,6. 1. Reproductive and Genetic Hospital of Citic-Xiangya, ChangSha, 410078, China. 2. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, ChangSha, 410078, China. 3. Laboratory of Reproductive and Stem Cell Engineering, National Health and Family Planning Commission, ChangSha, 410078, China. 4. Reproductive and Genetic Hospital of Citic-Xiangya, ChangSha, 410078, China. linggf@hotmail.com. 5. Institute of Reproductive and Stem Cell Engineering, School of Basic Medical Science, Central South University, ChangSha, 410078, China. linggf@hotmail.com. 6. Laboratory of Reproductive and Stem Cell Engineering, National Health and Family Planning Commission, ChangSha, 410078, China. linggf@hotmail.com.
Abstract
PURPOSE: To investigate the pathogenesis of the recurrent preimplantation embryonic arrest characterized by direct cleavage. METHODS: Two affected individuals underwent time-lapse imaging to observe the cleavage behaviors in their final ICSI attempts. In addition, both patients were subjected to whole-exome sequencing. After the identification of possible causative genes, molecular modeling analyses were used to evaluate the possible effects of candidate mutations on protein secondary structure. RESULTS: All the bipronucleated (2PN) zygotes from both individuals presented multiple abnormal cleavage behaviors, particularly direct cleavage (DC) and subsequent cleavage arrest. Mutation analysis identified one new frameshift mutation c.1521dupC (p.S508Qfs*5) and two missense mutations c.A1117C and c.C1708T (p.T373P and p.R570C, respectively) of the PADI6 gene, which were in the protein-arginine deiminase (PAD) domain and highly conserved. CONCLUSION: This study expands the mutation spectrum of PADI6 and is the first to propose that the preimplantation embryonic arrest with concomitant abnormal cleavage behaviors, especially DC, maybe associated with PADI6 mutations.
PURPOSE: To investigate the pathogenesis of the recurrent preimplantation embryonic arrest characterized by direct cleavage. METHODS: Two affected individuals underwent time-lapse imaging to observe the cleavage behaviors in their final ICSI attempts. In addition, both patients were subjected to whole-exome sequencing. After the identification of possible causative genes, molecular modeling analyses were used to evaluate the possible effects of candidate mutations on protein secondary structure. RESULTS: All the bipronucleated (2PN) zygotes from both individuals presented multiple abnormal cleavage behaviors, particularly direct cleavage (DC) and subsequent cleavage arrest. Mutation analysis identified one new frameshift mutation c.1521dupC (p.S508Qfs*5) and two missense mutations c.A1117C and c.C1708T (p.T373P and p.R570C, respectively) of the PADI6 gene, which were in the protein-arginine deiminase (PAD) domain and highly conserved. CONCLUSION: This study expands the mutation spectrum of PADI6 and is the first to propose that the preimplantation embryonic arrest with concomitant abnormal cleavage behaviors, especially DC, maybe associated with PADI6 mutations.
Entities:
Keywords:
Direct cleavage; Mutation; PADI6; Preimplantation embryonic arrest
Authors: D Bebbere; A Abazari-Kia; S Nieddu; B Melis Murgia; D F Albertini; S Ledda Journal: J Assist Reprod Genet Date: 2020-07-01 Impact factor: 3.412