A novel TLE6 mutation, c.541+1G>A, identified using whole‐exome sequencing in a Chinese family with female infertility. Issue 8 (15th July 2021)

• Record Type: Journal Article
• Authors: Mao, Bin; Jia, Xueling; Liu, Hongfang; Xu, Xiaojuan; Zhao, Xiaodong; Yuan, Yue; Li, Hongxing; Ma, Xiaoling; Zhang, Lili
• Is Part Of: Molecular genetics & genomic medicine. Volume 9:Issue 8(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-07-15
• Subjects: female infertility -- ICSI -- IVF -- mutation -- TLE6 mutation; Medical genetics -- Periodicals; Genomics -- Periodicals; 616.042
• DOI: 10.1002/mgg3.1743
• Languages: English
• ISSNs: 2324-9269

Abstract

Abstract: Background: Oocytes have a lot of maternal RNAs and proteins, which are used by the early embryo before zygotic genome activation. Transducin‐like enhancer of split 6 (TLE6) is a component of a subcortical maternal complex which plays a critical role in early embryonic development. Methods: The patient had been diagnosed with primary infertility for 6 years and had undergone multiple failed in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) cycles. Genomic DNA samples were extracted from her parents' peripheral blood as well as hers. Whole‐exome sequencing and Sanger validation were performed to identify candidate variants. Results: We identified a novel transducin‐like enhancer of split 6 ( TLE6 ) gene mutations in the female patient with recurrent IVF/ICSI failure. The patient carried a homozygous mutation (NM_001143986.1( TLE6 ): c.541+1G>A) and had viable but low‐quality embryos. Her parents both had heterozygous mutations at this locus. Conclusion: Our study expands the mutational and phenotypic spectrum of TLE6 and suggests the important role of TLE6 during embryonic development. Our findings have implications for the genetic diagnosis of female infertility with recurrent IVF/ICSI failure. Abstract : Our study identified a novel mutation in TLE6 associated with early embryonic arrest and thus expanded the mutational spectrum of TLE6 and the phenotypic spectrum of patients with such mutations. Our findings add new information on the genetic basis of female infertility and suggest that TLE6 might be a therapeutic target as well as genetic diagnostic marker for recurrent IVF/ICSI failure.