ArticleGenome biology2015
TLE6 mutation causes the earliest known human embryonic lethality.
Article in Genome biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 108 papers, 2 of them syntheses that pooled it.
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Who cites it
108 citing papers in PubMed, 2 syntheses or guidelines pooled it, 218 citations in OpenAlex.
- Molecular Drivers of Developmental Arrest in the Human Preimplantation Embryo: A Systematic Review and Critical Analysis Leading to Mapping Future Research.International journal of molecular sciences · 2021Pooled it
- The genetic architecture of sporadic and multiple consecutive miscarriage.Nature communications · 2020Pooled it
- Cytoplasmic lattices store developmentally poised degradative and cytoskeletal complexes in mammalian eggs.Nature structural & molecular biology · 2026Article
- The importance of integrating genetic testing into reproductive medicine: a retrospective observational study investigating the monogenic causes of human infertility in couples considering ICSI.Journal of human genetics · 2026Observational
- Novel mutations in NLRP2 and NLRP7 cause early embryonic arrest and female infertility.Journal of assisted reproduction and genetics · 2026Article
- Review
- The cytoplasmic lattice in mammalian eggs sequesters ubiquitination machinery and tubulin in reserve.bioRxiv : the preprint server for biology · 2026Article
- Genetic Mutations and Non-Genomic Dysregulation in Human Preimplantation Embryo Arrest.International journal of molecular sciences · 2026Review
- A simple, efficient, and scalable method to generate oocyte-like cells in vitro.Life science alliance · 2026Article
- Case Report: BiallelicFrontiers in genetics · 2026Article
- DNA Methylation Variation in Blood Cells may Impact Platelet Function.TH open : companion journal to thrombosis and haemostasis · 2026Article
- Meiotic gene variants contribute to recurrent blastulation failure.Human reproduction open · 2026Article
- Novel mutations in transducin-like enhancer of split 6 cause infertility in women with embryonic arrest.Journal of assisted reproduction and genetics · 2025Article
- Novel homozygous variants in ASTL and WEE2 responsible for female infertility characterized by abnormal fertilization.Journal of assisted reproduction and genetics · 2025Article
- An Nlrp5-null mutation leads to attenuated de novo methylation in oocytes, accompanied by a significant reduction in DNMT3L.Molecular human reproduction · 2025Article
- Maternal loss of mouse Nlrp2 alters the transcriptome and DNA methylome in GV oocytes and impairs zygotic genome activation in embryos.Clinical epigenetics · 2025Article
- Identification of novel variants and expansion of the phenotypic spectrum in PATL2, WEE2, and TUBB8 associated with human early embryonic arrest.Journal of assisted reproduction and genetics · 2025Article
- Evaluation of Risk Factors and a Gene Panel as a Tool for Unexplained Infertility Diagnosis by Next-Generation Sequencing.Medicina (Kaunas, Lithuania) · 2025Review
- Subcortical Maternal Complex in Female Infertility: A Transition from Animal Models to Human Studies.Molecular biology reports · 2025Review
- Identification of a novel TLE6 mutation linked to embryonic arrest and limited rescue by mRNA supplementation.Frontiers in medicine · 2025Article
48 more citing papers are in PubMed but not listed here.
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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundEmbryonic lethality is a recognized phenotypic expression of individual gene mutations in model organisms. However, identifying embryonic lethal genes in humans is challenging, especially when the phenotype is manifested at the preimplantation stage.
resultsIn an ongoing effort to exploit the highly consanguineous nature of the Saudi population to catalog recessively acting embryonic lethal genes in humans, we have identified two families with a female-limited infertility phenotype. Using autozygosity mapping and whole exome sequencing, we map this phenotype to a single mutation in TLE6, a maternal effect gene that encodes a member of the subcortical maternal complex in mammalian oocytes. Consistent with the published phenotype of mouse Tle6 mutants, embryos from female patients who are homozygous for the TLE6 mutation fail to undergo early cleavage, with resulting sterility. The human mutation abrogates TLE6 phosphorylation, a step that is reported to be critical for the PKA-mediated progression of oocyte meiosis II. Furthermore, the TLE6 mutation impairs its binding to components of the subcortical maternal complex.
conclusionIn this first report of a human defect in a member of the subcortical maternal subcritical maternal complex, we show that the TLE6 mutation is gender-specific and leads to the earliest known human embryonic lethality phenotype.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.