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Genetic screening and analysis of TUBB8 variants in females seeking ART

  • Author Footnotes
    # These authors contributed equally to this work.
    Tingting Lin
    Footnotes
    # These authors contributed equally to this work.
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China

    Chongqing Key Laboratory of Human Embryo Engineering Chongqing, China
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  • Author Footnotes
    # These authors contributed equally to this work.
    Weiwei Liu
    Footnotes
    # These authors contributed equally to this work.
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China
    Search for articles by this author
  • Wei Han
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China
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  • Keya Tong
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China
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  • Yezhou Xiang
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China
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  • Haiyuan Liao
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China
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  • Ke Chen
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China
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  • Yao He
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China
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  • Dongyun Liu
    Correspondence
    Corresponding authors.
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China
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  • Guoning Huang
    Correspondence
    Corresponding authors.
    Affiliations
    Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University Chongqing, China

    Chongqing Health Center for Women and Children Chongqing, China

    Chongqing Key Laboratory of Human Embryo Engineering Chongqing, China
    Search for articles by this author
  • Author Footnotes
    # These authors contributed equally to this work.
Published:October 16, 2022DOI:https://doi.org/10.1016/j.rbmo.2022.10.008

      Abstract

      Research question: More than 100 variants have been identified in the TUBB8 gene, which account for approximately 30% of infertile women with oocyte maturation defects. But what is the correlation between the highly phenotypic diversity and genetic variability? Are there other variants in TUBB8 related to female infertility?
      Design: TUBB8 resequencing was performed in 80 female subjects who were experiencing infertility and were seeking treatment with assisted reproductive technologies (ART), or had ever experienced ART failure due to oocyte maturation defects. All variants were evaluated with pedigree analysis, population frequency, in-silico analysis and molecular modelling. The effects of the variants on oocytes/arrested embryos were assessed by morphological observations, immunostaining, embryo biopsies and chromosome euploidy analysis.
      Results: Nine missense variants and two frameshift variants from an additional 15 families were identified, including four novel variants and seven previously reported recurrent variants. These TUBB8 variants were related to highly variable phenotypes, including abnormalities in oocyte maturation or morphology, fertilization failure, embryonic development abnormalities and implantation failure. Also further clarified were the incomplete penetrance of heterozygous p.E108K, the likely benign significance of heterozygous p.A313V and the clinical effect of a novel variant of p.R380C.
      Conclusions: This study significantly expands the variant spectrum of the TUBB8 gene and, together with the available findings on TUBB8 variants and female infertility, will potentially facilitate the genetic counselling of infertile women in future.

      Keywords

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      References

        • Alpha Scientists in Reproductive Medicine and ESHRE Special Interest Group Embryology
        The Istanbul consensus workshop on embryo assessment: proceedings of an expert meeting.
        Hum. Reprod. 2011; 26: 1270-1283https://doi.org/10.1093/humrep/der037
        • Cao T.
        • Guo J.
        • Xu Y.
        • Lin X.
        • Deng W.
        • Cheng L.
        • Zhao H.
        • Jiang S.
        • Gao M.
        • Huang J.
        • Xu Y.
        Two mutations inTUBB8 cause developmental arrest in human oocytes and early embryos.
        Reprod. Biomed. Online. 2021; 43: 891-898https://doi.org/10.1016/j.rbmo.2021.07.020
        • Chen B.
        • Li B.
        • Li D.
        • Yan Z.
        • Mao X.
        • Xu Y.
        • Mu J.
        • Li Q.
        • Jin L.
        • He L.
        • Kuang Y.
        • Sang Q.
        • Wang L.
        Novel mutations and structural deletions inTUBB8: expanding mutational and phenotypic spectrum of patients with arrest in oocyte maturation, fertilization or early embryonic development.
        Hum. Reprod. 2017; 32: 457-464https://doi.org/10.1093/humrep/dew322
        • Chen B.
        • Wang W.
        • Peng X.
        • Jiang H.
        • Zhang S.
        • Li D.
        • Li B.
        • Fu J.
        • Kuang Y.
        • Sun X.
        • Wang X.
        • Zhang Z.
        • Wu L.
        • Zhou Z.
        • Lyu Q.
        • Yan Z.
        • Mao X.
        • Xu Y.
        • Mu J.
        • Li Q.
        • Jin L.
        • He L.
        • Sang Q.
        • Wang L.
        The comprehensive mutational and phenotypic spectrum ofTUBB8 in female infertility.
        Eur. J. Hum. Genet. 2019; 27: 300-307https://doi.org/10.1038/s41431-018-0283-3
        • Chen B.
        • Zhang Z.
        • Sun X.
        • Kuang Y.
        • Mao X.
        • Wang X.
        • Yan Z.
        • Li B.
        • Xu Y.
        • Yu M.
        • Fu J.
        • Mu J.
        • Zhou Z.
        • Li Q.
        • Jin L.
        • He L.
        • Sang Q.
        • Wang L.
        Biallelic mutations inPATL2 cause female infertility characterized by oocyte maturation arrest.
        Am. J. Hum. Genet. 2017; 101: 609-615https://doi.org/10.1016/j.ajhg.2017.08.018
        • Chen T.
        • Bian Y.
        • Liu X.
        • Zhao S.
        • Wu K.
        • Yan L.
        • Li M.
        • Yang Z.
        • Liu H.
        • Zhao H.
        • Chen Z.J.
        A recurrent missense mutation inZP3 causes empty follicle syndrome and female infertility.
        Am. J. Hum. Genet. 2017; 101: 459-465https://doi.org/10.1016/j.ajhg.2017.08.001
        • Coticchio G.
        • Dal Canto M.
        • Mignini Renzini M.
        • Guglielmo M.C.
        • Brambillasca F.
        • Turchi D.
        • Novara P.V.
        • Fadini R.
        Oocyte maturation: gamete-somatic cells interactions, meiotic resumption, cytoskeletal dynamics and cytoplasmic reorganization.
        Hum. Reprod. Update. 2015; 21: 427-454https://doi.org/10.1093/humupd/dmv011
        • Feng R.
        • Sang Q.
        • Kuang Y.
        • Sun X.
        • Yan Z.
        • Zhang S.
        • Shi J.
        • Tian G.
        • Luchniak A.
        • Fukuda Y.
        • Li B.
        • Yu M.
        • Chen J.
        • Xu Y.
        • Guo L.
        • Qu R.
        • Wang X.
        • Sun Z.
        • Liu M.
        • Shi H.
        • Wang H.
        • Feng Y.
        • Shao R.
        • Chai R.
        • Li Q.
        • Xing Q.
        • Zhang R.
        • Nogales E.
        • Jin L.
        • He L.
        • Gupta Jr., M.L.
        • Cowan N.J.
        • Wang L.
        Mutations inTUBB8 and human oocyte meiotic arrest.
        N. Engl. J. Med. 2016; 374: 223-232https://doi.org/10.1056/NEJMoa1510791
        • Feng R.
        • Yan Z.
        • Li B.
        • Yu M.
        • Sang Q.
        • Tian G.
        • Xu Y.
        • Chen B.
        • Qu R.
        • Sun Z.
        • Sun X.
        • Jin L.
        • He L.
        • Kuang Y.
        • Cowan N.J.
        • Wang L.
        Mutations inTUBB8 cause a multiplicity of phenotypes in human oocytes and early embryos.
        J. Med. Genet. 2016; 53: 662-671https://doi.org/10.1136/jmedgenet-2016-103891
        • Gardner D.K.
        • Lane M.
        Culture and selection of viable blastocysts: a feasible proposition for human IVF?.
        Hum. Reprod. Update. 1997; 3: 367-382https://doi.org/10.1093/humupd/3.4.367
        • Holubcova Z.
        • Blayney M.
        • Elder K.
        • Schuh M.
        Human oocytes. Error-prone chromosome-mediated spindle assembly favors chromosome segregation defects in human oocytes.
        Science. 2015; 348: 1143-1147https://doi.org/10.1126/science.aaa9529
        • Huang H.L.
        • Lv C.
        • Zhao Y.C.
        • Li W.
        • He X.M.
        • Li P.
        • Sha A.G.
        • Tian X.
        • Papasian C.J.
        • Deng H.W.
        • Lu G.X.
        • Xiao H.M.
        MutantZP1 in familial infertility.
        N. Engl. J. Med. 2014; 370: 1220-1226https://doi.org/10.1056/NEJMoa1308851
        • Huang L.
        • Tong X.
        • Luo L.
        • Zheng S.
        • Jin R.
        • Fu Y.
        • Zhou G.
        • Li D.
        • Liu Y.
        Mutation analysis of theTUBB8 gene in nine infertile women with oocyte maturation arrest.
        Reprod. Biomed. Online. 2017; 35: 305-310https://doi.org/10.1016/j.rbmo.2017.05.017
        • Huo M.
        • Zhang Y.
        • Shi S.
        • Shi H.
        • Liu Y.
        • Zhang L.
        • Wang Y.
        • Niu W.
        Gene spectrum and clinical traits of nine patients with oocyte maturation arrest.
        Front Genet. 2022; 13772143https://doi.org/10.3389/fgene.2022.772143
        • Janke C.
        The tubulin code: molecular components, readout mechanisms, and functions.
        J. Cell. Biol. 2014; 206: 461-472https://doi.org/10.1083/jcb.201406055
        • Jia Y.
        • Li K.
        • Zheng C.
        • Tang Y.
        • Bai D.
        • Yin J.
        • Chi F.
        • Zhang Y.
        • Li Y.
        • Tu Z.
        • Wang Y.
        • Pan J.
        • Liang S.
        • Guo Y.
        • Ruan J.
        • Kong P.
        • Wu B.
        • Hu Y.
        • Wang H.
        • Liu W.
        • Teng X.
        • Gao S.
        Identification and rescue of a novelTUBB8 mutation that causes the first mitotic division defects and infertility.
        J. Assist. Reprod. Genet. 2020; 37: 2713-2722https://doi.org/10.1007/s10815-020-01945-w
        • Lanuza-Lopez M.C.
        • Martinez-Garza S.G.
        • Solorzano-Vazquez J.F.
        • Paz-Cervantes D.
        • Gonzalez-Ortega C.
        • Maldonado-Rosas I.
        • Villegas-Moreno G.
        • Villar-Munoz L.G.
        • Arroyo-Mendez F.A.
        • Gutierrez-Gutierrez A.M.
        • Pina-Aguilar R.E.
        Oocyte maturation arrest produced byTUBB8 mutations: impact of genetic disorders in infertility treatment.
        Gynecol. Endocrinol. 2020; 36: 829-834https://doi.org/10.1080/09513590.2020.1725968
        • Li R.
        • Albertini D.F.
        The road to maturation: somatic cell interaction and self-organization of the mammalian oocyte.
        Nat. Rev. Mol. Cell. Biol. 2013; 14: 141-152https://doi.org/10.1038/nrm3531
        • Liu W.
        • Li K.
        • Bai D.
        • Yin J.
        • Tang Y.
        • Chi F.
        • Zhang L.
        • Wang Y.
        • Pan J.
        • Liang S.
        • Guo Y.
        • Ruan J.
        • Kou X.
        • Zhao Y.
        • Wang H.
        • Chen J.
        • Teng X.
        • Gao S.
        Dosage effects ofZP2 andZP3 heterozygous mutations cause human infertility.
        Hum. Genet. 2017; 136: 975-985https://doi.org/10.1007/s00439-017-1822-7
        • Liu Z.
        • Xi Q.
        • Zhu L.
        • Yang X.
        • Jin L.
        • Wang J.
        • Zhang T.
        • Zhou X.
        • Zhang D.
        • Peng X.
        • Luo Y.
        • Li Z.
        • Zhang X.
        TUBB8 mutations cause female infertility with large polar body oocyte and fertilization failure.
        Reprod. Sci. 2021; 28: 2942-2950https://doi.org/10.1007/s43032-021-00633-z
        • Lu Q.
        • Zhang X.
        • Cao Q.
        • Wang C.
        • Ding J.
        • Zhao C.
        • Zhang J.
        • Ling X.
        • Meng Q.
        • Huo R.
        • Li H.
        Expanding the genetic and phenotypic spectrum of female infertility caused byTUBB8 mutations.
        Reprod. Sci. 2021; 28: 3448-3457https://doi.org/10.1007/s43032-021-00694-0
        • Maddirevula S.
        • Coskun S.
        • Al-Qahtani M.
        • Aboyousef O.
        • Alhassan S.
        • Aldeery M.
        • Alkuraya F.S.
        ASTL is mutated in female infertility.
        Hum. Genet. 2022; 141: 49-54https://doi.org/10.1007/s00439-021-02388-8
        • Mullen T.J.
        • Davis-Roca A.C.
        • Wignall S.M.
        Spindle assembly and chromosome dynamics during oocyte meiosis.
        Curr. Opin. Cell. Biol. 2019; 60: 53-59https://doi.org/10.1016/j.ceb.2019.03.014
        • Pacchiarotti A.
        • Selman H.
        • Valeri C.
        • Napoletano S.
        • Sbracia M.
        • Antonini G.
        • Biagiotti G.
        • Pacchiarotti A.
        Ovarian stimulation protocol in IVF: an up-to-date review of the literature.
        Curr. Pharm. Biotechnol. 2016; 17: 303-315https://doi.org/10.2174/1389201017666160118103147
        • Richani D.
        • Gilchrist R.B.
        Approaches to oocyte meiotic arrest in vitro and impact on oocyte developmental competence.
        Biol. Reprod. 2022; 106: 243-252https://doi.org/10.1093/biolre/ioab176
        • Richards S.
        • Aziz N.
        • Bale S.
        • Bick D.
        • Das S.
        • Gastier-Foster J.
        • Grody W.W.
        • Hegde M.
        • Lyon E.
        • Spector E.
        • Voelkerding K.
        • Rehm H.L.
        • Committee A.L.Q.A.
        Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
        Genet. Med. 2015; 17: 405-424https://doi.org/10.1038/gim.2015.30
        • Sang Q.
        • Li B.
        • Kuang Y.
        • Wang X.
        • Zhang Z.
        • Chen B.
        • Wu L.
        • Lyu Q.
        • Fu Y.
        • Yan Z.
        • Mao X.
        • Xu Y.
        • Mu J.
        • Li Q.
        • Jin L.
        • He L.
        • Wang L.
        Homozygous mutations inWEE2 cause fertilization failure and female infertility.
        Am. J. Hum. Genet. 2018; 102: 649-657https://doi.org/10.1016/j.ajhg.2018.02.015
        • Sang Q.
        • Zhang Z.
        • Shi J.
        • Sun X.
        • Li B.
        • Yan Z.
        • Xue S.
        • Ai A.
        • Lyu Q.
        • Li W.
        • Zhang J.
        • Wu L.
        • Mao X.
        • Chen B.
        • Mu J.
        • Li Q.
        • Du J.
        • Sun Q.
        • Jin L.
        • He L.
        • Zhu S.
        • Kuang Y.
        • Wang L.
        A pannexin 1 channelopathy causes human oocyte death.
        Sci. Transl. Med. 2019; 11https://doi.org/10.1126/scitranslmed.aav8731
        • Severson A.F.
        • von Dassow G.
        • Bowerman B.
        Oocyte meiotic spindle assembly and function.
        Curr. Top Dev. Biol. 2016; 116: 65-98https://doi.org/10.1016/bs.ctdb.2015.11.031
        • Sha Q.
        • Zheng W.
        • Feng X.
        • Yuan R.
        • Hu H.
        • Gong F.
        • Hu L.
        • Lin G.
        • Ou X.
        Novel mutations inTUBB8 expand the mutational and phenotypic spectrum of patients with zygotes containing multiple pronuclei.
        Gene. 2021; 769145227https://doi.org/10.1016/j.gene.2020.145227
        • Sha Q.Q.
        • Zhang J.
        • Fan H.Y.
        A story of birth and death: mRNA translation and clearance at the onset of maternal-to-zygotic transition in mammals.
        Biol. Reprod. 2019; 101: 579-590https://doi.org/10.1093/biolre/ioz012
        • Wang A.C.
        • Zhang Y.S.
        • Wang B.S.
        • Zhao X.Y.
        • Wu F.X.
        • Zhai X.H.
        • Sun J.X.
        • Mei S.Y.
        Mutation analysis of theTUBB8 gene in primary infertile women with arrest in oocyte maturation.
        Gynecol. Endocrinol. 2018; 34: 900-904https://doi.org/10.1080/09513590.2018.1464138
        • Wang W.
        • Dong J.
        • Chen B.
        • Du J.
        • Kuang Y.
        • Sun X.
        • Fu J.
        • Li B.
        • Mu J.
        • Zhang Z.
        • Zhou Z.
        • Lin Z.
        • Wu L.
        • Yan Z.
        • Mao X.
        • Li Q.
        • He L.
        • Wang L.
        • Sang Q.
        Homozygous mutations inREC114 cause female infertility characterised by multiple pronuclei formation and early embryonic arrest.
        J. Med. Genet. 2020; 57: 187-194https://doi.org/10.1136/jmedgenet-2019-106379
        • Wang W.
        • Wang W.
        • Xu Y.
        • Shi J.
        • Fu J.
        • Chen B.
        • Mu J.
        • Zhang Z.
        • Zhao L.
        • Lin J.
        • Du J.
        • Li Q.
        • He L.
        • Jin L.
        • Sun X.
        • Wang L.
        • Sang Q.
        FBXO43 variants in patients with female infertility characterized by early embryonic arrest.
        Hum. Reprod. 2021; 36: 2392-2402https://doi.org/10.1093/humrep/deab131
        • Xiang J.
        • Wang W.
        • Qian C.
        • Xue J.
        • Wang T.
        • Li H.
        • Li H.
        Human oocyte maturation arrest caused by a novel missense mutation inTUBB8.
        J. Int. Med. Res. 2018; 46: 3759-3764https://doi.org/10.1177/0300060518778638
        • Xing Q.
        • Wang R.
        • Chen B.
        • Li L.
        • Pan H.
        • Li T.
        • Ma X.
        • Cao Y.
        • Wang B.
        Rare homozygous mutation inTUBB8 associated with oocyte maturation defect-2 in a consanguineous mating family.
        J. Ovarian Res. 2020; 13: 42https://doi.org/10.1186/s13048-020-00637-4
        • Yan L.
        • Yang M.
        • Guo H.
        • Yang L.
        • Wu J.
        • Li R.
        • Liu P.
        • Lian Y.
        • Zheng X.
        • Yan J.
        • Huang J.
        • Li M.
        • Wu X.
        • Wen L.
        • Lao K.
        • Li R.
        • Qiao J.
        • Tang F.
        Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells.
        Nat. Struct. Mol. Biol. 2013; 20: 1131-1139https://doi.org/10.1038/nsmb.2660
        • Yang P.
        • Yin C.
        • Li M.
        • Ma S.
        • Cao Y.
        • Zhang C.
        • Chen T.
        • Zhao H.
        Mutation analysis of tubulin beta 8 class VIII in infertile females with oocyte or embryonic defects.
        Clin. Genet. 2021; 99: 208-214https://doi.org/10.1111/cge.13855
        • Yao Z.
        • Zeng J.
        • Zhu H.
        • Zhao J.
        • Wang X.
        • Xia Q.
        • Li Y.
        • Wu L.
        Mutation analysis of theTUBB8 gene in primary infertile women with oocyte maturation arrest.
        J. Ovarian Res. 2022; 15: 38https://doi.org/10.1186/s13048-022-00971-9
        • Yu C.
        • Ji S.Y.
        • Sha Q.Q.
        • Sun Q.Y.
        • Fan H.Y.
        CRL4-DCAF1 ubiquitin E3 ligase directs protein phosphatase 2A degradation to control oocyte meiotic maturation.
        Nat. Commun. 2015; 6: 8017https://doi.org/10.1038/ncomms9017
        • Yuan H.
        • Chen J.
        • Li N.
        • Miao H.
        • Chen Y.
        • Lyu S.
        • Qiao Y.
        • Yang G.
        • Luo H.
        • Chen L.
        • Mao F.
        • Huang L.
        • He Y.
        • Hu S.
        • Miao C.
        • Qian Y.
        • Feng R.
        Target-sequencing of female infertility pathogenic gene panel and a novelTUBB8 loss-of-function mutation.
        Front Genet. 2022; 13865103https://doi.org/10.3389/fgene.2022.865103
        • Yuan P.
        • Zheng L.
        • Liang H.
        • Li Y.
        • Zhao H.
        • Li R.
        • Lai L.
        • Zhang Q.
        • Wang W.
        A novel mutation in theTUBB8 gene is associated with complete cleavage failure in fertilized eggs.
        J. Assist. Reprod. Genet. 2018; 35: 1349-1356https://doi.org/10.1007/s10815-018-1188-3
        • Zhang X.
        • Liang B.
        • Xu X.
        • Zhou F.
        • Kong L.
        • Shen J.
        • Xia Y.
        • Xuan L.
        • Mao Y.
        • Xue Y.
        • Liu C.
        • Tan J.
        The comparison of the performance of four whole genome amplification kits on ion proton platform in copy number variation detection.
        Biosci. Rep. 2017; 37https://doi.org/10.1042/BSR20170252
        • Zhang Z.
        • Li B.
        • Fu J.
        • Li R.
        • Diao F.
        • Li C.
        • Chen B.
        • Du J.
        • Zhou Z.
        • Mu J.
        • Yan Z.
        • Wu L.
        • Liu S.
        • Wang W.
        • Zhao L.
        • Dong J.
        • He L.
        • Liang X.
        • Kuang Y.
        • Sun X.
        • Sang Q.
        • Wang L.
        Bi-allelic missense pathogenic variants inTRIP13 cause female infertility characterized by oocyte maturation arrest.
        Am. J. Hum. Genet. 2020; 107: 15-23https://doi.org/10.1016/j.ajhg.2020.05.001
        • Zhao L.
        • Guan Y.
        • Wang W.
        • Chen B.
        • Xu S.
        • Wu L.
        • Yan Z.
        • Li B.
        • Fu J.
        • Shi R.
        • Shi J.
        • Du J.
        • Li Q.
        • Zhang Z.
        • Mu J.
        • Zhou Z.
        • Dong J.
        • Jin L.
        • He L.
        • Sun X.
        • Kuang Y.
        • Wang L.
        • Sang Q.
        Identification novel mutations inTUBB8 in female infertility and a novel phenotype of large polar body in oocytes withTUBB8 mutations.
        J. Assist. Reprod. Genet. 2020; 37: 1837-1847https://doi.org/10.1007/s10815-020-01830-6
        • Zheng W.
        • Hu H.
        • Zhang S.
        • Xu X.
        • Gao Y.
        • Gong F.
        • Lu G.
        • Lin G.
        The comprehensive variant and phenotypic spectrum ofTUBB8 in female infertility.
        J. Assist. Reprod. Genet. 2021; 38: 2261-2272https://doi.org/10.1007/s10815-021-02219-9
        • Zheng W.
        • Zhou Z.
        • Sha Q.
        • Niu X.
        • Sun X.
        • Shi J.
        • Zhao L.
        • Zhang S.
        • Dai J.
        • Cai S.
        • Meng F.
        • Hu L.
        • Gong F.
        • Li X.
        • Fu J.
        • Shi R.
        • Lu G.
        • Chen B.
        • Fan H.
        • Wang L.
        • Lin G.
        • Sang Q.
        Homozygous mutations inBTG4 cause zygotic cleavage failure and female infertility.
        Am. J. Hum. Genet. 2020; 107: 24-33https://doi.org/10.1016/j.ajhg.2020.05.010

      Biography

      Guoning Huang is Chairman of the Chinese Society of Reproductive Medicine (CSRM) and is Director of the Center for Reproductive Medicine, Women and Children's Hospital of Chongqing Medical University. His research areas are the genetic factors underlying primary female and male infertility and exploring the feasible clinical methods for these patients.
      Key message
      This study identified four novel variants and seven previously reported variants in the TUBB8 gene. It further clarified the highly variable phenotypes related to these variants, especially of p.E108K, p.A313V and a novel variant of p.R380C. These findings significantly extend the variant spectrum of the TUBB8 gene and will potentially facilitate the genetic counselling of infertile women.