ArticleGenetics in medicine : official journal of the American College of Medical Genetics2020
De novo SMARCA2 variants clustered outside the helicase domain cause a new recognizable syndrome with intellectual disability and blepharophimosis distinct from Nicolaides-Baraitser syndrome.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 51 citations in OpenAlex.
- Blended Phenotypes in Siblings: Dual Diagnoses of Nicolaides-Baraitser and Craniosynostosis Syndromes.Molecular syndromology · 2026Article
- Genotypic and Phenotypic Profile of 50 Cases With Chromatin Remodeling Complexes-Related Neurological Disorders.CNS neuroscience & therapeutics · 2026Article
- Diagnostic Pitfall in Genomic Era: DiscordantDiagnostics (Basel, Switzerland) · 2026Article
- A study of sex-specific genetic effects underlying risk of orofacial clefts also highlights the potential impact of sequencing errors due to short read mis-mapping.medRxiv : the preprint server for health sciences · 2026Article
- Unraveling the layers of epigenetic control in respiratory antiviral defense.Journal of virology · 2026Review
- Episignature leads to diagnosis and reclassification of DYRK1A variant in a child with syndromic neurodevelopmental disorder: a case report.Frontiers in genetics · 2026Article
- Analysis Methods for Diagnosing Rare Neurodevelopmental Diseases with Episignatures: A Systematic Review of the Literature.Biomedicines · 2025Review
- ARID2-related disorder: further delineation of the clinical phenotype of 27 novel individuals and description of an epigenetic signature.European journal of human genetics : EJHG · 2025Article
- Whole-genome sequencing reveals individual and cohort level insights into chromosome 9p syndromes.Genome medicine · 2025Article
- CUX1 variant and 9p deletion: expanding the spectrum and resolving variable GDD/ID in a family.BMC medical genomics · 2025Article
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- Artificial intelligence-driven genotype-epigenotype-phenotype approaches to resolve challenges in syndrome diagnostics.EBioMedicine · 2025Article
- Molecular and clinical aspects of histone-related disorders.Human genomics · 2025Review
- Clinical and genetic delineation of autosomal recessive and dominant ACTL6B-related developmental brain disorders.Genetics in medicine : official journal of the American College of Medical Genetics · 2025Article
- SWI/SNF Complex Connects Signaling and Epigenetic State in Cells of Nervous System.Molecular neurobiology · 2025Review
- Optical genome mapping uncovers clinically relevant structural variants in congenital heart disease with heterotaxy.Frontiers in genetics · 2025Article
- Diagnostic utility of DNA methylation analysis in genetically unsolved pediatric epilepsies and CHD2 episignature refinement.Nature communications · 2024Article
- A novel SMARCC1 BAFopathy implicates neural progenitor epigenetic dysregulation in human hydrocephalus.Brain : a journal of neurology · 2024Article
- Epigenetic regulation of craniofacial development and disease.Birth defects research · 2024Review
- PLS3 missense variants affecting the actin-binding domains cause X-linked congenital diaphragmatic hernia and body-wall defects.American journal of human genetics · 2023Article
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Authors and funding
48 authors at 20 institutions in 9 countries.
Funding
Abstract
purposeNontruncating variants in SMARCA2, encoding a catalytic subunit of SWI/SNF chromatin remodeling complex, cause Nicolaides-Baraitser syndrome (NCBRS), a condition with intellectual disability and multiple congenital anomalies. Other disorders due to SMARCA2 are unknown.
methodsBy next-generation sequencing, we identified candidate variants in SMARCA2 in 20 individuals from 18 families with a syndromic neurodevelopmental disorder not consistent with NCBRS. To stratify variant interpretation, we functionally analyzed SMARCA2 variants in yeasts and performed transcriptomic and genome methylation analyses on blood leukocytes.
resultsOf 20 individuals, 14 showed a recognizable phenotype with recurrent features including epicanthal folds, blepharophimosis, and downturned nasal tip along with variable degree of intellectual disability (or blepharophimosis intellectual disability syndrome [BIS]). In contrast to most NCBRS variants, all SMARCA2 variants associated with BIS are localized outside the helicase domains. Yeast phenotype assays differentiated NCBRS from non-NCBRS SMARCA2 variants. Transcriptomic and DNA methylation signatures differentiated NCBRS from BIS and those with nonspecific phenotype. In the remaining six individuals with nonspecific dysmorphic features, clinical and molecular data did not permit variant reclassification.
conclusionWe identified a novel recognizable syndrome named BIS associated with clustered de novo SMARCA2 variants outside the helicase domains, phenotypically and molecularly distinct from NCBRS.
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