ArticleHuman genomics2019
EFTUD2 gene deficiency disrupts osteoblast maturation and inhibits chondrocyte differentiation via activation of the p53 signaling pathway.
Article in Human genomics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 29 citations in OpenAlex.
- Recurrent mandibulofacial dysostosis, Guion-Almeida type in consecutive pregnancies due to maternal mosaicism of a novel EFTUD2 variant: a case report and review of the literature.Journal of medical case reports · 2026Review
- Mechanistic study of antisense long non-coding RNAExploration of targeted anti-tumor therapy · 2026Article
- Complex de novo structural variants are an underestimated cause of rare disorders.Nature communications · 2025Article
- A novelTranslational pediatrics · 2025Article
- Addressing the tissue specificity of U5 snRNP spliceosomopathies.Frontiers in cell and developmental biology · 2025Article
- A validated heart-specific model for splice-disrupting variants in childhood heart disease.Genome medicine · 2024Article
- Atypical mandibulofacial dysostosis with microcephaly diagnosed through the identification of a novel pathogenic mutation in EFTUD2.Molecular genetics & genomic medicine · 2024Article
- A common cellular response to broad splicing perturbations is characterized by metabolic transcript downregulation driven by the Mdm2-p53 axis.Disease models & mechanisms · 2024Article
- Weighted gene co-expression network analysis reveals the hub genes associated with pulmonary hypertension.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- The emerging significance of splicing in vertebrate development.Development (Cambridge, England) · 2022Review
- Craniofacial Defects in Embryos with Homozygous Deletion ofInternational journal of molecular sciences · 2022Article
- The Core Splicing Factors EFTUD2, SNRPB and TXNL4A Are Essential for Neural Crest and Craniofacial Development.Journal of developmental biology · 2022Article
- Research on the Mechanism of Kaempferol for Treating Senile Osteoporosis by Network Pharmacology and Molecular Docking.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- [Clinical case analysis and literature review of mandibulofacial dysostosis with microcephaly syndrome].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2022Review
- Mutation in Eftud2 causes craniofacial defects in mice via mis-splicing of Mdm2 and increased P53.Human molecular genetics · 2021Article
- Zebrafish Models for Human Skeletal Disorders.Frontiers in genetics · 2021Review
- Network Pharmacology Integrated with Molecular Docking Explores the Mechanisms of Naringin against Osteoporotic Fracture by Regulating Oxidative Stress.Evidence-based complementary and alternative medicine : eCAM · 2021Article
- Amniotic Fluid Stem Cell-Derived Extracellular Vesicles Counteract Steroid-Induced Osteoporosis In Vitro.International journal of molecular sciences · 2020Article
- Novel Splice Site Pathogenic Variant ofDiagnostics (Basel, Switzerland) · 2020Article
- Modelling the developmental spliceosomal craniofacial disorder Burn-McKeown syndrome using induced pluripotent stem cells.PloS one · 2020Article
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Authors and funding
9 authors at 4 institutions in 1 country.
Funding
Abstract
backgroundMandibulofacial dysostosis with microcephaly (MFDM) is characteristic of multiple skeletal anomalies comprising craniofacial anomalies/dysplasia, microcephaly, dysplastic ears, choanal atresia, and short stature. Heterozygous loss of function variants of EFTUD2 was previously reported in MFDM; however, the mechanism underlying EFTUD2-associated skeletal dysplasia remains unclear.
resultsWe identified a novel frameshift variant of EFTUD2 (c.1030_1031delTG, p.Trp344fs*2) in an MFDM Chinese patient with craniofacial dysmorphism including ear canal structures and microcephaly, mild intellectual disability, and developmental delay. We generated a zebrafish model of eftud2 deficiency, and a consistent phenotype consisting of mandibular bone dysplasia and otolith loss was observed. We also showed that EFTUD2 deficiency significantly inhibited proliferation, differentiation, and maturation in human calvarial osteoblast (HCO) and human articular chondrocyte (HC-a) cells. RNA-Seq analysis uncovered activated TP53 signaling with increased phosphorylation of the TP53 protein and upregulation of five TP53 downstream target genes (FAS, STEAP3, CASP3, P21, and SESN1) both in HCO and in eftud2-/- zebrafish. Additionally, inhibition of p53 by morpholino significantly reduced the mortality of eftud2-/- larvae.
conclusionsOur results confirm a novel de novo variant of the EFTUD2 gene and suggest that EFTUD2 may participate in the maturation and differentiation of osteoblasts and chondrocytes, possibly via activation of the TP53 signaling pathway. Thus, mutations in this gene may lead to skeletal anomalies in vertebrates.
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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.