{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nTUBB8 is a primate‐specific β‐tubulin isotype that is uniquely expressed in oocytes and early embryos, where it constitutes almost the entirety of the available β‐tubulin pool. In these cells, TUBB8 plays a critical role in the formation of the microtubule network by participating in the assembly of the α/β–tubulin heterodimer, which is essential for spindle formation and normal meiotic progression. Its spatially and temporally restricted expression underscores its importance in ensuring proper oocyte maturation and early embryonic development."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMutations in TUBB8 have been shown to disrupt chaperone-dependent folding and the subsequent assembly of the α/β–tubulin heterodimer, thereby impairing microtubule behavior. Such disruptions lead to catastrophic defects in the spindle apparatus that manifest as oocyte meiotic arrest, fertilization failure, and early embryonic arrest. Furthermore, these mutations have been associated with other abnormal phenotypes, including the formation of abnormally large polar bodies, cleavage failure and even abnormal pronuclei (multi-pronuclei) formation in zygotes. These findings indicate that TUBB8 variants exert dominant negative effects that are central to the pathogenesis of several forms of female infertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nRecent studies have expanded both the mutational and phenotypic spectrum of TUBB8. A large number of novel heterozygous and homozygous missense mutations, as well as frameshift variants, have been reported in patients with diverse clinical phenotypes ranging from oocyte maturation arrest to failure of embryo implantation. Functional assays, including in vitro microtubule dynamics analyses and investigations in cultured cells, have consistently demonstrated that these mutations cause abnormal microtubule network organization and spindle assembly defects. Moreover, efforts to optimize embryo culture conditions offer hope for rescue in some cases, emphasizing the clinical relevance of TUBB8 variant screening in the genetic diagnosis and management of female infertility."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "23"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Ruizhi Feng, Qing Sang, Yanping Kuang, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Novel variants in TUBB8 gene cause multiple phenotypic abnormalities in human oocytes and early embryos."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Ovarian Res (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1186/s13048-023-01274-3"}], "href": "https://doi.org/10.1186/s13048-023-01274-3"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "38007525"}], "href": "https://pubmed.ncbi.nlm.nih.gov/38007525"}]}]}]}