Mutation analysis of the TUBB8 gene in primary infertile women with arrest in oocyte maturation

Abstract

Tubulin beta eight class VIII (TUBB8) is a subtype of β-tubulin that only exists in primates. Mutations in the TUBB8 gene have been proven to cause oocyte maturation arrest. The aim of this study was to identify the new types of mutations in TUBB8. Six women (families) with oocyte maturation arrest and 100 healthy controls were recruited. The sequence of the TUBB8 gene was amplified and analyzed by Sanger sequencing, which revealed a de novo heterozygous variant c.292G > A (p.G98R) of TUBB8 in one affected individual. This TUBB8 variant was absent in the 100 fertile females and was predicted to be highly damaging to the function of the TUBB8 protein by SIFT and PolyPhen-2. This novel variant extends the spectrum of TUBB8 mutations and the presence of a TUBB8 mutation is being considered to be indicative of a poor prognosis for the success of assisted reproductive treatment.

Chinese abstract

β微管蛋白VIII (TUBB8)为β-微管蛋白的一个亚型, 仅存在于灵长类动物中。现已证实TUBB8基因突变可导致卵母细胞成熟障碍。本研究的目的是确定新的TUBB8变异类型。招募了6例确诊卵母细胞成熟障碍的女性（家庭）和100位健康对照组。通过Sanger测序对TUBB8基因序列进行扩增和分析, 在一位受试对象的TUBB8中揭示了一种得新杂合变异c. 292G>A (p.G98R)。这种TUBB8变异在100位生育能力正常的对照组中是不存在的, 并且通过SIFT和polyphen2预测这种变异会对TUBB8蛋白的功能造成严重的损害。这种新的变异扩展了TUBB8突变的范围, 而TUBB8突变的存在被认为预示着辅助生殖治疗的不良结局。

Keywords:

• Female infertility
• oocyte maturation arrest
• TUBB8 gene
• mutation

Acknowledgments

The authors thank Prof. Lei Wang (State Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai, PR China) for support.

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

The study was supported by the Shandong Provincial Natural Science Foundation, China [ZR2016HP37], the National Natural Science Fund of China [81501620] and the Shandong Provincial Medical Health Science and Technology Development Project, China [2015WS0377, 2013WS0077].