Ping Yuan1, Lingyan Zheng1, Hao Liang2, Yu Li1, Haijing Zhao1, Ruiqi Li1, Luhua Lai2,3, Qingxue Zhang1, Wenjun Wang4. 1. IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang Xi Road, Guangzhou, 510120, Guangdong, China. 2. Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, 100871, China. 3. Beijing National Laboratory for Molecular Sciences, State Key Laboratory for Structural Chemistry of Unstable and Stable Species, College of Chemistry and Molecular Engineering, Peking University, Beijing, 100871, China. 4. IVF Center, Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital, Sun Yat-Sen University, 107 Yanjiang Xi Road, Guangzhou, 510120, Guangdong, China. wenjungzcn@163.com.
Abstract
PURPOSE: Cleavage of the zygote during human reproduction is a key event of early embryonic development. The genetic events associated with idiopathic embryonic cleavage failure are not certain. Mutations in the tubulin beta 8 class VIII (TUBB8) gene have been reported to be associated with oocyte maturation, fertilization, and developmental arrest. Here, we aimed to assess the clinical and genetic characteristics of complete cleavage failure in fertilized eggs. METHODS: We have characterized a patient with a 9-year history of primary infertility in a non-consanguineous family from China. The patient presented complete cleavage failure in all two-pronuclear (2PN) fertilized oocytes after 2 cycles of in vitro fertilization (IVF). We performed Sanger sequencing of the TUBB8 gene in the patient, and further bioinformatics analysis to identify pathogenesis of gene. RESULTS: A novel homozygous mutation, c.322G > A (p.Glu108Lys), was detected, and this change was absent from 179 control subjects. Glutamic acid is highly conserved at this position, and replacement by lysine was predicted to be repelled by the α-tubulin positive region, disrupting the α-β tubulin interaction. CONCLUSIONS: Our findings presented a homozygous mutation of TUBB8 associated with complete cleavage failure in fertilized eggs and provided new data for the genotype-phenotype of TUBB8-related diseases.
PURPOSE: Cleavage of the zygote during human reproduction is a key event of early embryonic development. The genetic events associated with idiopathic embryonic cleavage failure are not certain. Mutations in the tubulin beta 8 class VIII (TUBB8) gene have been reported to be associated with oocyte maturation, fertilization, and developmental arrest. Here, we aimed to assess the clinical and genetic characteristics of complete cleavage failure in fertilized eggs. METHODS: We have characterized a patient with a 9-year history of primary infertility in a non-consanguineous family from China. The patient presented complete cleavage failure in all two-pronuclear (2PN) fertilized oocytes after 2 cycles of in vitro fertilization (IVF). We performed Sanger sequencing of the TUBB8 gene in the patient, and further bioinformatics analysis to identify pathogenesis of gene. RESULTS: A novel homozygous mutation, c.322G > A (p.Glu108Lys), was detected, and this change was absent from 179 control subjects. Glutamic acid is highly conserved at this position, and replacement by lysine was predicted to be repelled by the α-tubulin positive region, disrupting the α-β tubulin interaction. CONCLUSIONS: Our findings presented a homozygous mutation of TUBB8 associated with complete cleavage failure in fertilized eggs and provided new data for the genotype-phenotype of TUBB8-related diseases.
Authors: Biaobang Chen; Bin Li; Da Li; Zheng Yan; Xiaoyan Mao; Yao Xu; Jian Mu; Qiaoli Li; Li Jin; Lin He; Yanping Kuang; Qing Sang; Lei Wang Journal: Hum Reprod Date: 2016-12-17 Impact factor: 6.918