ArticleAmerican journal of human genetics2020
Homozygous Mutations in BTG4 Cause Zygotic Cleavage Failure and Female Infertility.
Article in American journal of human genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 57 papers.
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Who cites it
57 citing papers in PubMed, 114 citations in OpenAlex.
- Pathogenicity assessment of genetic variants in reproductive disorders.Journal of assisted reproduction and genetics · 2026Review
- Novel biallelic PATL2 variants causing predominant germinal vesicle arrest and recurrent ART failure: expanded mutational spectrum and evidence-based reproductive counseling guidance.Journal of assisted reproduction and genetics · 2026Article
- Spontaneous natural conception and live birth in three patients with likely pathogenic variants in TUBB8, ZP2, and ZP3 associated with female subfertility.Journal of ovarian research · 2026Article
- The SPN-4 Rbfox RNA-binding protein selects maternal mRNAs for CCR4-NOT-dependent clearance in early Caenorhabditis elegans embryos.Development (Cambridge, England) · 2026Article
- CCDC174 deficiency impaired human fertility by affecting the alternative splicing of maternal mRNAs.EMBO molecular medicine · 2026Article
- THAP1 is a maternal effect factor required for the first cell cycle via Rrm1 in early mouse embryos.EMBO reports · 2026Article
- Human YTHDC2 mutations disturb RNA homeostasis of oocytes and early embryos.Human genetics · 2026Article
- Multi-omics biomarkers in female fertility: from oocyte quality to endometrial receptivity and clinical translation.Biomarker research · 2026Review
- Article
- Genetic Mutations and Non-Genomic Dysregulation in Human Preimplantation Embryo Arrest.International journal of molecular sciences · 2026Review
- Novel missense variants in COX15 cause oocyte degeneration and female infertility.Journal of assisted reproduction and genetics · 2026Article
- Autophagy regulates the maternal-to-zygotic transition through MAP1LC3B-mediated maternal mRNA decay.Autophagy · 2026Article
- Genetic landscape of human oocyte/embryo defects.Cell genomics · 2026Article
- Meiotic gene variants contribute to recurrent blastulation failure.Human reproduction open · 2026Article
- ZAR1 pathogenic variants disrupt maternal mRNA storage and cause oocyte maturation defects in humans.Cellular and molecular life sciences : CMLS · 2025Article
- The SPN-4 Rbfox RNA-binding protein selects maternal mRNAs for CCR4-NOT-dependent clearance in earlybioRxiv : the preprint server for biology · 2025Article
- Homozygous variant in JARID2 causes female infertility characterized by compromised blastulation efficiency.Journal of ovarian research · 2025Article
- PAL-AI reveals genetic determinants that control poly(A)-tail length during oocyte maturation, with relevance to human fertility.Nature communications · 2025Article
- PABPN1 Couples the Polyadenylation and Translation of Maternal Transcripts to Mouse Oocyte Meiotic Maturation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- The maternal-to-zygotic transition: reprogramming of the cytoplasm and nucleus.Nature reviews. Genetics · 2025Review
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Authors and funding
22 authors at 10 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Zygotic cleavage failure (ZCF) is a unique early embryonic phenotype resulting in female infertility and recurrent failure of in vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI). With this phenotype, morphologically normal oocytes can be retrieved and successfully fertilized, but they fail to undergo cleavage. Until now, whether this phenotype has a Mendelian inheritance pattern and which underlying genetic factors play a role in its development remained to be elucidated. B cell translocation gene 4 (BTG4) is a key adaptor of the CCR4-NOT deadenylase complex, which is involved in maternal mRNA decay in mice, but no human diseases caused by mutations in BTG4 have previously been reported. Here, we identified four homozygous mutations in BTG4 (GenBank: NM_017589.4) that are responsible for the phenotype of ZCF, and we found they followed a recessive inheritance pattern. Three of them-c.73C>T (p.Gln25Ter), c.1A>G (p.?), and c.475_478del (p.Ile159LeufsTer15)-resulted in complete loss of full-length BTG4 protein. For c.166G>A (p.Ala56Thr), although the protein level and distribution of mutant BTG4 was not altered in zygotes from affected individuals or in HeLa cells, the interaction between BTG4 and CNOT7 was abolished. In vivo studies further demonstrated that the process of maternal mRNA decay was disrupted in the zygotes of the affected individuals, which provides a mechanistic explanation for the phenotype of ZCF. Thus, we provide evidence that ZCF is a Mendelian phenotype resulting from mutations in BTG4. These findings contribute to our understanding of the role of BTG4 in human early embryonic development and provide a genetic marker for female infertility.
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