期刊
REPRODUCTIVE SCIENCES
卷 28, 期 12, 页码 3448-3457出版社
SPRINGER HEIDELBERG
DOI: 10.1007/s43032-021-00694-0
关键词
Female infertility; Tubulin beta 8 class VIII; Mutations; Whole-exome sequencing
资金
- National Key Research and Development Program of China [2018YFC1004002]
- National Natural Science Foundation of China [31671556]
- Key talents ofmaternal and child health in the second cycle of Jiangsu Province [FRC201725]
In this study, five heterozygous variants of the TUBB8 gene were identified in infertile patients, with two of the variants confirmed to be associated with infertility phenotypes through in vitro experiments. The results expand the range of TUBB8 variants and phenotypic spectrum related to female infertility.
Tubulin beta eight class VIII (TUBB8) is a subtype of beta-tubulin that only exists in primates. TUBB8 mutations have been reported to cause arrest of oocyte maturation and embryonic development. We aim to further investigate the mutational spectrum of TUBB8 and its relevance with female infertility. In our study, infertile patients were recruited, and their basal and clinical characteristics were analyzed. Genomic DNA was extracted from peripheral blood donated by patients. Candidate variants were identified by whole-exome sequencing, selected by relevant criteria, and validated by Sanger sequencing. We found five heterozygous variants: c.C208A(p.P70T), c.T907C(p.C303R), c.G173A(p.R58K), c.G326T(p.G109V), and c.C916T(p.R306C) in TUBB8 among six infertile patients characterized by abnormal phenotypes in oocyte maturation, fertilization, or embryo development. Most of oocytes retrieved from affected individuals were arrested at GV (germinal vesicle) stage and early embryos were arrested at variable stages. In vitro experiments were performed, and the relationship between variant c.G173A(p.R58K), c.C208A(p.P70T), and infertility phenotype was confirmed. We also discussed the possibility about patient II-1 from family 4 is affected by germinal/germline mosaicism. These results expand the kinds of variants and phenotypic spectrum of TUBB8 variants with regard to female infertility.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据