A novel homozygous C-terminal deletion in BTG4 causes zygotic cleavage failure and female infertility
A novel homozygous C-terminal deletion in BTG4 causes zygotic cleavage failure and female infertility
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DOI：
10.1007/s10815-022-02664-0
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发表时间：
2022-12
影响因子：
3.1
通讯作者：
Yufen Wang;Qingtao Qin;Yang Yang-Yang;Shan Dong;Yuting Liu;Molin Wang;Yongxin Zou;Y. Gong;Haibin Zhou;Baichun Jiang
中科院分区：
文献类型：
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作者：
Yufen Wang;Qingtao Qin;Yang Yang-Yang;Shan Dong;Yuting Liu;Molin Wang;Yongxin Zou;Y. Gong;Haibin Zhou;Baichun Jiang
PurposeWe旨在确定致病性变异的女性患者原发性不孕症和反复失败的体外受精与合子卵裂failure.MethodsThe基因组DNA从受影响的个人进行全外显子组测序和变异证实桑格测序。在293 T cells.ResultsWe确定了一种新的纯合性缺失inBTG 4（c.580_616del）在受影响的个人的功能效果进一步研究了所确定的变体。该缺失导致移码和用66个随机氨基酸替换最后29个残基（aa 195 -223）。突变的氨基酸残基在哺乳动物物种中高度保守。293 T细胞免疫共沉淀实验结果表明，该突变消除了BTG 4与PABPN 1 L的相互作用。我们的研究结果证明了BTG 4的C-末端的功能重要性。BTG 4是一个潜在的诊断和治疗合子卵裂失败患者的目标。
PurposeWe aimed to identify pathogenic variants in a female patient with primary infertility and recurrent failure of in vitro fertilization with zygotic cleavage failure.MethodsThe genomic DNA from the affected individual was subjected to whole-exome sequencing and the variant was confirmed by Sanger sequencing. The functional effect of the identified variant was further investigated in 293 T cells.ResultsWe identified a novel homozygous deletion inBTG4(c.580_616del) in the affected individual. The deletion results in frameshift and replacement of the last 29 residues (aa195-223) with 66 random amino acids. The mutated amino acid residues are highly conserved among mammalian species. Co-immunoprecipitation in 293 T cells showed that the mutation abolished the interaction between BTG4 and PABPN1L.ConclusionThis study conforms previous studies and expands the mutational spectrum ofBTG4. Our findings prove the functional importance of the C-terminal of BTG4.BTG4is a potential diagnostic and therapeutic target for patients suffering from zygotic cleavage failure.