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Mutation analysis of tubulin beta 8 class VIII in infertile females with oocyte or embryonic defects
Author(s) -
Yang Ping,
Yin Changjian,
Li Mei,
Ma Shuiying,
Cao Yongzhi,
Zhang Changming,
Chen Tailai,
Zhao Han
Publication year - 2021
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13855
Subject(s) - pronucleus , oocyte , biology , missense mutation , sanger sequencing , genetics , frameshift mutation , human fertilization , embryogenesis , andrology , oocyte activation , phenotype , infertility , embryonic stem cell , embryo , mutation , zygote , gene , medicine , pregnancy
Variants of tubulin beta 8 class VIII ( TUBB8 ) have been shown to be associated with female infertility characterized by oocyte or embryonic defects. To further investigate the mutational spectrum of TUBB8 and the prevalence of variants, we performed Sanger sequencing of TUBB8 on a total of 115 infertile females who had undergone repeated in vitro fertilization cycles with oocyte or embryonic defects and 200 healthy controls. A total of 31 variants which were absent from the controls were identified in 36 unrelated individuals, accounting for a large proportion of this cohort (31.3%). All of the variants including heterozygous/homozygous missense variants and a heterozygous frameshift insertion variant were at conserved sites and predicted to be deleterious. Besides, these variants had diverse phenotypic effects, including not only oocyte maturation arrest, fertilization failure, and early embryonic arrest, but also multi‐pronuclei (MPN) formation, which is a new phenotype associated with TUBB8 variants. Overall, this study reveals a large number of variants of the TUBB8 gene in infertile females with oocyte or embryonic defects. Our results not only broaden the mutational and phenotypic spectra of TUBB8 variants, but also further confirm the critical role of TUBB8 in oocyte maturation, fertilization, and early embryonic development.