Purpose

We aimed to identify novel variants in TUBB8 and corresponding new abnormal phenotypes in oocytes/fertilization/ embryonic development responsible for female infertility.

Methods

Sanger sequencing of TUBB8 was performed in infertile women with abnormalities in oocyte maturation or embryonic development. The effects of the variants were evaluated in patients’ oocytes by morphological observations and immunofluorescence.

Results

We identified 34 novel variants of TUBB8 in 51 patients who were diagnosed with abnormalities in oocyte maturation or early embryonic development. We found a novel phenotype in which large polar bodies were present in three independent patients possibly associated with a recurrent variant. Moreover, we identified a novel type of TUBB8 variant consisting of an in-frame deletion-insertion, which has not been previously reported.

Conclusions

Our present study identified 34 novel variants in TUBB8 in 51 patients. These patients show oocyte maturation arrest, oocytes with large polar body, fertilization failure, early embryonic arrest or embryonic implantation failure. These results expand the kinds of variants and phenotypic spectrum of TUBB8 variants with regard to female infertility.

中文翻译：

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鉴定女性不育症中 TUBB8 的新突变和具有 TUBB8 突变的卵母细胞中大极体的新表型。

目的

我们旨在确定TUBB8 中的新变体以及导致女性不育的卵母细胞/受精/胚胎发育中相应的新异常表型。

方法

TUBB8 的Sanger 测序是在卵母细胞成熟或胚胎发育异常的不育女性中进行的。通过形态学观察和免疫荧光在患者的卵母细胞中评估了变体的影响。

结果

我们在 51 名被诊断为卵母细胞成熟或早期胚胎发育异常的患者中发现了 34 种新型TUBB8变异。我们发现了一种新的表型，其中大极体存在于三名可能与复发性变异相关的独立患者中。此外，我们确定了一种新型的TUBB8变体，它由帧内删除插入组成，以前从未报道过。

结论

我们目前的研究在 51 名患者中发现了TUBB8中的34 个新变异。这些患者表现出卵母细胞成熟停滞、卵母细胞具有大的极体、受精失败、早期胚胎停滞或胚胎着床失败。这些结果扩展了TUBB8变体在女性不育方面的变体种类和表型谱。