ArticleGenetics in medicine : official journal of the American College of Medical Genetics2023
Rare variants found in clinical gene panels illuminate the genetic and allelic architecture of orofacial clefting.
Article in Genetics in medicine : official journal of the American College of Medical Genetics, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Comprehensive analysis ofmedRxiv : the preprint server for health sciences · 2026Article
- Actomyosin contractility and a threshold of cadherin cell adhesion are required during tissue fusion.The Journal of cell biology · 2026Article
- Haploinsufficiency of GRHL2 is associated with orofacial clefting in humans.Human molecular genetics · 2025Article
- Distinguishing syndromic and nonsyndromic cleft palate through analysis of protein-altering de novo variants in 818 trios.American journal of human genetics · 2025Article
- Meta-analysis reveals transcription factors and DNA binding domain variants associated with congenital heart defect and orofacial cleft.NPJ genomic medicine · 2025Article
- Exome Sequencing Reveals the Genetic Architecture of Non-syndromic Orofacial Clefts and Identifies BOC as a Novel Causal Gene.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Functional Annotation of De Novo Variants Found Near GWAS Loci Associated With Cleft Lip With or Without Cleft Palate.Birth defects research · 2025Article
- The power of mouse models in the diagnostic odyssey of patients with rare congenital anomalies.Mammalian genome : official journal of the International Mammalian Genome Society · 2025Review
- Gene expression patterns of the developing human face at single cell resolution reveal cell type contributions to normal facial variation and disease risk.bioRxiv : the preprint server for biology · 2025Article
- Four putative pathogenic ARHGAP29 variants in patients with non-syndromic orofacial clefts (NsOFC).European journal of human genetics : EJHG · 2025Article
- Functional analysis of ESRP1/2 gene variants and CTNND1 isoforms in orofacial cleft pathogenesis.Communications biology · 2024Article
- Functional analysis ofbioRxiv : the preprint server for biology · 2024Article
- Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference?American journal of medical genetics. Part A · 2023Article
- Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference?medRxiv : the preprint server for health sciences · 2023Article
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23 authors.
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Abstract
purposeOrofacial clefts (OFCs) are common birth defects including cleft lip, cleft lip and palate, and cleft palate. OFCs have heterogeneous etiologies, complicating clinical diagnostics because it is not always apparent if the cause is Mendelian, environmental, or multifactorial. Sequencing is not currently performed for isolated or sporadic OFCs; therefore, we estimated the diagnostic yield for 418 genes in 841 cases and 294 controls.
methodsWe evaluated 418 genes using genome sequencing and curated variants to assess their pathogenicity using American College of Medical Genetics criteria.
results9.04% of cases and 1.02% of controls had "likely pathogenic" variants (P < .0001), which was almost exclusively driven by heterozygous variants in autosomal genes. Cleft palate (17.6%) and cleft lip and palate (9.09%) cases had the highest yield, whereas cleft lip cases had a 2.80% yield. Out of 39 genes with likely pathogenic variants, 9 genes, including CTNND1 and IRF6, accounted for more than half of the yield (4.64% of cases). Most variants (61.8%) were "variants of uncertain significance", occurring more frequently in cases (P = .004), but no individual gene showed a significant excess of variants of uncertain significance.
conclusionThese results underscore the etiological heterogeneity of OFCs and suggest sequencing could reduce the diagnostic gap in OFCs.
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