ArticleHuman molecular genetics2019
A de novo substitution in BCL11B leads to loss of interaction with transcriptional complexes and craniosynostosis.
Article in Human molecular genetics, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers, 2 of them syntheses that pooled it.
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Who cites it
27 citing papers in PubMed, 2 syntheses or guidelines pooled it, 32 citations in OpenAlex.
- BCL11B-related disease: a single phenotypic entity?European journal of human genetics : EJHG · 2025Pooled it
- Review of Recurrently Mutated Genes in Craniosynostosis Supports Expansion of Diagnostic Gene Panels.Genes · 2023Pooled it
- Signalling Pathways and Mechanical Forces Interact in Craniofacial Development and Homeostasis.International dental journal · 2026Review
- Bcl11b dose-dependently regulates positive selection of CD8 T cells to the virtual memory fate.bioRxiv : the preprint server for biology · 2026Article
- Bipartite DNA binding domain of transcription factor BCL11B binds clustered short DNA sequence motifs.bioRxiv : the preprint server for biology · 2026Article
- A novel heterozygous mutation of BCL11B gene causes neurodevelopmental disorder and middle type hypospadias in a Chinese boy with 5 years follow-up.Neurogenetics · 2026Article
- Unraveling the molecular landscape of congenital pseudoarthrosis of the tibia: insights from a comprehensive analysis of 159 probands.Orphanet journal of rare diseases · 2025Article
- DNA-binding affinity and specificity determine the phenotypic diversity in BCL11B-related disorders.American journal of human genetics · 2025Article
- Evaluation of the etiology of epilepsy and/or developmental delay in children via next-generation sequencing: a single-center experience.Frontiers in pediatrics · 2025Article
- [BCL11B associated disorder a case report in Mexican population. Case report].Revista medica del Instituto Mexicano del Seguro Social · 2024Article
- Pivotal role of BCL11B in the immune, hematopoietic and nervous systems: a review of the BCL11B-associated phenotypes from the genetic perspective.Genes and immunity · 2024Review
- Review
- Transcriptional regulation in the development and dysfunction of neocortical projection neurons.Neural regeneration research · 2024Review
- Article
- Joint multi-ancestry and admixed GWAS reveals the complex genetics behind human cranial vault shape.Nature communications · 2023Review
- Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis.Current issues in molecular biology · 2023Review
- Further validation of craniosynostosis as a part of phenotypic spectrum of BCL11B-related BAFopathy.American journal of medical genetics. Part A · 2023Article
- Multisuture craniosynostosis: a case report of unusual presentation of chromosome 14q32 deletion.Child's nervous system : ChNS : official journal of the International Society for Pediatric Neurosurgery · 2023Article
- Novel BCL11B truncation variant in a patient with developmental delay, distinctive features, and early craniosynostosis.Human genome variation · 2022Article
- Case report: A novel truncating variant ofFrontiers in pediatrics · 2022Article
Corrections and comments
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Authors and funding
17 authors at 4 institutions in 4 countries.
Funding
Abstract
Craniosynostosis, the premature ossification of cranial sutures, is a developmental disorder of the skull vault, occurring in approximately 1 in 2250 births. The causes are heterogeneous, with a monogenic basis identified in ~25% of patients. Using whole-genome sequencing, we identified a novel, de novo variant in BCL11B, c.7C>A, encoding an R3S substitution (p.R3S), in a male patient with coronal suture synostosis. BCL11B is a transcription factor that interacts directly with the nucleosome remodelling and deacetylation complex (NuRD) and polycomb-related complex 2 (PRC2) through the invariant proteins RBBP4 and RBBP7. The p.R3S substitution occurs within a conserved amino-terminal motif (RRKQxxP) of BCL11B and reduces interaction with both transcriptional complexes. Equilibrium binding studies and molecular dynamics simulations show that the p.R3S substitution disrupts ionic coordination between BCL11B and the RBBP4-MTA1 complex, a subassembly of the NuRD complex, and increases the conformational flexibility of Arg-4, Lys-5 and Gln-6 of BCL11B. These alterations collectively reduce the affinity of BCL11B p.R3S for the RBBP4-MTA1 complex by nearly an order of magnitude. We generated a mouse model of the BCL11B p.R3S substitution using a CRISPR-Cas9-based approach, and we report herein that these mice exhibit craniosynostosis of the coronal suture, as well as other cranial sutures. This finding provides strong evidence that the BCL11B p.R3S substitution is causally associated with craniosynostosis and confirms an important role for BCL11B in the maintenance of cranial suture patency.
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Registered trials
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.