Department of Genetics, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
Molecular Genetics Laboratory, Molecular Diagnostics Division, London Health Sciences Centre, London, Ontario, Canada; Department of Pathology and Laboratory Medicine, Western University, London, Ontario, Canada.
Reprod Biomed Online. 2023 Oct;47(4):103226. doi: 10.1016/j.rbmo.2023.04.017. Epub 2023 May 3.
Are TUBB8 gene variations present in Iranian infertile women with oocyte maturation arrest or embryo cleavage arrest?
TUBB8 gene variations were investigated by polymerase chain reaction sequencing on blood samples from 16 women with oocyte maturation arrest and 12 women with cleavage arrest, collectively referred to as the experimental cohort, as well as 56 fertile women as the control group. The Exome Sequencing Project and dbSNP databases and the Genome Aggregation Database were used to search the frequency of corresponding variants. PolyPhen and SIFT were used to conduct in-silico analysis of gene variations and Align-GVGD was used to predict the effect of missense variants on proteins. The homology modelling and structure evaluation of variations was also checked.
Two likely pathogenic variants [c.713C>T (p.Thr238Met), c.1054G>T (p.Ala352Ser)] were identified in patients with oocyte maturation arrest and one likely pathogenic variant [c.G763A, (p.Val255Met)] was identified in a patient with cleavage arrest. These changes were absent in controls.
Three deleterious variants in TUBB8 related to oocyte maturation arrest or cleavage arrest and infertility were identified. TUBB8 variant screening for patients with oocyte maturation and cleavage arrest is recommended.
伊朗卵母细胞成熟阻滞或胚胎卵裂阻滞的不孕女性是否存在 TUBB8 基因突变？
通过聚合酶链反应测序，对 16 例卵母细胞成熟阻滞和 12 例卵裂阻滞的女性（统称为实验组）以及 56 例正常生育女性（对照组）的血液样本进行 TUBB8 基因突变检测。使用 Exome Sequencing Project 和 dbSNP 数据库以及 Genome Aggregation Database 来搜索相应变异的频率。使用 PolyPhen 和 SIFT 进行基因变异的计算机分析，使用 Align-GVGD 预测错义变异对蛋白质的影响。还检查了变异的同源建模和结构评估。
在卵母细胞成熟阻滞患者中发现了两个可能的致病性变异[c.713C>T(p.Thr238Met), c.1054G>T(p.Ala352Ser)]，在卵裂阻滞患者中发现了一个可能的致病性变异[c.G763A(p.Val255Met)]。这些变化在对照组中不存在。
鉴定出与卵母细胞成熟阻滞或卵裂阻滞及不孕相关的 TUBB8 中的三个有害变异。建议对卵母细胞成熟阻滞和卵裂阻滞的患者进行 TUBB8 变异筛查。
