Cleft Lip and Palate Research

Characterization of de novo structural variants in trios with orofacial clefts

This study identifies de novo structural variants in individuals with orofacial clefts and finds they contribute to genetic risk, with some variants disrupting known risk genes and suggesting new candidate genes.

Heterochronic Uncoupling of Brain and Face Morphogenesis Drives Premature Fusion in Ciliary Transition Zone Mutants

The paper shows that reduced brain growth in ciliary transition zone mutants causes premature facial fusion by mechanically forcing facial prominences into convergence.

OFC-SV: Interpreting structural variants in African and Asian cohorts with non-syndromic orofacial clefts

OFC-SV is a web portal that interprets structural variants in genomic data from African and Asian cohorts with non-syndromic orofacial clefts, identifying 41 novel SV genes and their regulatory impacts.

Trio-based GWAS reveals novel loci associated with different forms of isolated cleft lip

The paper performs trio-based GWAS on cleft lip subtypes to identify novel genetic loci associated with specific phenotypes.

Common Variant Contributions to Neurodevelopmental Risk in Orofacial Clefts

The paper investigates whether common genetic variants contribute to neurodevelopmental risks in children with cleft lip/palate, finding no strong genetic correlation with psychiatric traits but noting independent clinical relevance of polygenic risk scores.

The XenCart Protocol: A Method for Alcian Blue Labeling and Quantitative Analysis of Craniofacial Cartilage in Xenopus

The XenCart Protocol quantifies craniofacial cartilage in Xenopus to study environmental effects, showing e-liquid exposure reduces cartilage dimensions and alters morphology.

Leveraging the genetics of human face shape boosts the discovery of orofacial cleft risk loci

This study uses a pleiotropy-informed GWAS method to identify new orofacial cleft risk loci by leveraging genetic associations with facial shape.

Time-resolved inference of gene regulatory networks underlying human cranial neural crest development suggests novel risk genes for orofacial clefting.

Association of DOT1L histone methyltransferase with non-syndromic orofacial clefts in a cohort of children of African and Asian ancestry

The paper identifies structural variants in the DOT1L locus associated with non-syndromic orofacial clefts in children of African and Asian ancestry, supporting an oligogenic model for cleft lip/palate susceptibility.

Methylation quantitative loci analysis in nonsyndromic orofacial clefts

The paper identifies methylation quantitative loci (meQTLs) associated with nonsyndromic orofacial clefts, linking genetic variants to epigenetic changes that may explain missing heritability.

The ectodermal loss of ARHGAP29 alters epithelial morphology and organization and disrupts murine palatal development

This study shows that loss of ARHGAP29 in mice causes delayed palatal shelf fusion and cleft palate by altering epithelial morphology and increasing contractility proteins.

Retinoid signaling promotes frontonasal identity while repressing maxillary identity during craniofacial development

This study shows retinoid signaling specifies frontonasal identity and represses maxillary identity in cranial neural crest cells during facial development in mice.

Comprehensive analysis of de novo variants across 2,497 orofacial cleft trios reveals novel genetic drivers of disease

This study identifies novel genetic drivers of orofacial clefts by analyzing de novo variants in 2,497 trios and integrating findings across subtypes and syndromic status.

Conservation of transcriptional regulatory networks in zebrafish and human periderm facilitates identification of GRHL1 as an orofacial cleft risk gene

The paper identifies GRHL1 as an orofacial cleft risk gene by analyzing conserved transcriptional regulatory networks between zebrafish and human periderm using single-cell multiome sequencing and functional validation.

Laterality, Symmetry and Completeness Patterns of Nonsyndromic Orofacial Clefts in a Multiethnic Cohort

The paper analyzes the laterality, symmetry, and completeness of nonsyndromic orofacial clefts in a multiethnic cohort, finding sex, race, and ethnicity influence these traits but not completeness.

Epigenetic Signatures in Monozygotic and Dizygotic Twins Discordant for Orofacial Clefts

The paper identifies differentially methylated CpG sites in twins discordant for NSCL/P, linking them to retinoic acid signaling and chromatin regulation.

A non-coding variant at 2p24.2 confers susceptibility to non-syndromic cleft lip and palate through LLPS-dependent regulation of MYCN

This study identifies a non-coding variant at 2p24.2 that increases susceptibility to NSCLP by disrupting FOXP2-mediated LLPS and impairing MYCN transcriptional activation.

Zfp750 prevents oral adhesions and promotes temporary epithelial fusions

The paper investigates the role of Zfp750 in periderm development and orofacial cleft risk by analyzing genetic variants and mouse models.

Notch signaling in the embryonic ectoderm promotes periderm cell fate and represses mineralization of vibrissa hair follicles

This study shows that Notch signaling in the embryonic ectoderm promotes periderm cell fate and prevents mineralization of vibrissa hair follicles, linking it to craniofacial development.

Genetic and Epigenetic Contributors to Cleft Laterality: Evidence from Monozygotic Mirror Twins and Replication Cohorts

This study identifies genetic and epigenetic factors contributing to cleft laterality using monozygotic twins and replication cohorts, finding methylation differences in ARID5B, ZFP57, and HOOK2 associated with cleft side and severity.

Maternal-fetal inflammation affects Cdh1/E-cadherin epigenetic regulation and craniofacial development

The paper investigates how maternal pro-inflammatory responses affect Cdh1/E-cadherin epigenetic regulation and craniofacial development in embryos.

Rare variants in PRKCI cause Van der Woude syndrome and other features of peridermopathy

The paper identifies rare variants in PRKCI as a novel cause of Van der Woude syndrome and other peridermopathy features through clinical and functional analyses.

Identification of novel genes regulating the development of the palate

The study identifies 45 novel genes involved in palate development using IMPC knockout mouse embryos and micro-CT data.

Genetic Heterogeneity and Homogeneity Among Orofacial Cleft Subtypes: Genome-Wide Association Studies in the Cleft Collective

This study conducts GWAS on orofacial cleft subtypes, identifying 27 genome-wide significant regions, including novel loci, and highlights genetic heterogeneity and homogeneity across subtypes.

Cell Cycle Arrest of a "Zippering" Epithelial Cell Cluster Shapes the Face and is Disrupted in Craniofacial Disorders

The paper identifies a novel epithelial population, Zippering Lambda, whose cell cycle arrest is critical for facial prominence fusion and is disrupted in orofacial clefting.

Gene-by-environment interactions involving maternal exposures with orofacial cleft risk in Filipinos

The paper investigates gene-environment interactions involving maternal exposures and orofacial cleft risk in Filipinos, identifying suggestive interactions with smoking and vitamin use.

Identification of functional non-coding variants associated with orofacial cleft

This study identifies functional non-coding variants associated with orofacial cleft by combining GWAS, reporter assays, and stem cell modeling.

Functional annotation of de novo variants found near GWAS loci associated with cleft lip with or without cleft palate

The paper annotates de novo variants near GWAS loci for cleft lip with or without cleft palate, finding noncoding variants in enhancer regions associated with craniofacial development genes.

Hypoxia impedes differentiation of cranial neural crest cells into derivatives relevant for craniofacial development

The paper shows hypoxia impairs differentiation of cranial neural crest cells into chondrocytes, osteoblasts, and smooth muscle cells, linking it to orofacial cleft risk.

Genetic Analysis and Functional Assessment of a TGFBR2 Variant in Micrognathia and Cleft Palate

The paper identifies a TGFBR2 variant in patients with micrognathia and cleft palate, tests its causality in mice, and finds it does not cause craniofacial anomalies, highlighting challenges in translating genetic findings to models.