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Expanding the phenotypic and genetic spectrum of TUBB8 in female infertility: Suggestions for genetic counseling
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  • Wei Zheng,
  • Shuoping Zhang,
  • Pingyuan Xie,
  • Huiling Hu,
  • Jing Dai,
  • Xilin Xu,
  • Yifan Gu,
  • Jia Wang,
  • Xiaofeng Li,
  • Yi Tang,
  • Hui Guo,
  • Liang Hu,
  • Fei Gong,
  • Guangxiu Lu,
  • Ge Lin
Wei Zheng
Reproductive and Genetic Hospital CITIC Xiangya
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Shuoping Zhang
Reproductive and Genetic Hospital CITIC Xiangya
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Pingyuan Xie
Hunan Normal University School of Medicine
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Huiling Hu
Central South University
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Jing Dai
Reproductive and Genetic Hospital CITIC Xiangya
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Xilin Xu
Reproductive and Genetic Hospital CITIC Xiangya
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Yifan Gu
Reproductive and Genetic Hospital CITIC Xiangya
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Jia Wang
Reproductive and Genetic Hospital CITIC Xiangya
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Xiaofeng Li
Reproductive and Genetic Hospital CITIC Xiangya
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Yi Tang
Reproductive and Genetic Hospital CITIC Xiangya
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Hui Guo
Reproductive and Genetic Hospital CITIC Xiangya
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Liang Hu
Central South University Xiangya School of Medicine
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Fei Gong
Reproductive and Genetic Hospital CITIC Xiangya
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Guangxiu Lu
Reproductive and Genetic Hospital CITIC Xiangya
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Ge Lin
CITIC Reproductive and Genetic Hospital Xiangya
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Abstract

Tubulin beta 8 class VII (TUBB8), a primate oocyte/embryo-specific β-tubulin isotype, is a preferentially analyzed gene in the genetic diagnosis of infertile women. Studies have currently identified 47 variants of this gene. However, the evaluation of its pathogenicity and the resulting phenotypes vary, and this gene requires further study in order to be included in genetic counseling analyses. We have performed a whole exome sequencing (WES) screening of 385 infertile female subjects and 400 controls, identifying 29 TUBB8 variants (of which 23 were novel). These variants may be responsible for female infertility, especially in the case of embryonic arrest, and their identification further expands the variant spectrum of TUBB8. Our findings are the first to report a new phenotype of large polar body in TUBB8 variant patients and determine some recurrent variants that were specific for complete cleavage failure. We have also illustrated some phenotypes of TUBB8 variant patients and recommended using computational modeling approach to assess the pathogenicity of novel TUBB8 variants, particularly for maternally inherited variants. Our studies will contribute in laying the foundation for the genetic counseling of infertile women in the future.