Cleft Lip and Palate Research

Single-cell multi-omics decodes regulatory programs during development of mouse secondary palate

This study uses single-cell multi-omics to map regulatory programs during mouse secondary palate development, identifying key transcription factors involved in anterior and posterior palatal mesenchymal differentiation.

Novel insights into the fundamentals of palatal shelf elevation dynamics in normal mouse embryos

This study reveals the dynamic timing and sex-specific differences in palatal shelf elevation in mouse embryos using high-resolution imaging.

A unique form of collective epithelial migration is crucial for tissue fusion in the secondary palate and can overcome loss of epithelial apoptosis

Kdm6b confers Tfdp1 with the competence to activate p53 signalling in regulating palatogenesis

This study identifies Kdm6b's role in regulating p53 signaling during palatogenesis by enabling Tfdp1 to activate p53 expression through chromatin accessibility.

Genome-wide interaction study implicates VGLL2 and alcohol exposure and PRL and smoking in orofacial cleft risk

The paper identifies gene-environment interactions associated with orofacial cleft risk, highlighting VGLL2 and PRL as key genes interacting with alcohol and smoking, respectively.

Srsf3 mediates alternative RNA splicing downstream of PDGFRα signaling

This study identifies Srsf3 as a regulator of alternative RNA splicing downstream of PDGFRα signaling, which is critical for craniofacial development.

FAT4 Identified as a Potential Modifier of Orofacial Cleft Laterality

The paper identifies a genetic modifier, FAT4, associated with left-sided cleft lip and palate, suggesting genetic factors differ from epidemiological patterns.

RELATIONSHIP BETWEEN PARENTAL AGE AND SEVERITY OF OROFACIAL CLEFTS

This study examines the relationship between parental age and severity of orofacial clefts, finding increased risk with older fathers and more severe clefts in older mothers.

The PAX1 locus at 20p11 is a modifier for bilateral cleft lip only

The paper investigates genetic differences between bilateral and unilateral cleft lip and palate subtypes using genome-wide association studies and finds distinct genetic architectures.

In-frame deletion of SPECC1L microtubule binding domain results in embryonic tissue movement and fusion defects

This study shows that in-frame deletions in the SPECC1L CCD2 domain cause embryonic tissue movement and fusion defects, leading to cleft palate and exencephaly, and identifies CCD2 as a gain-of-function mutation.

All-trans Retinoic Acid Regulates miR-106a-5p Inhibition of Autophagic in Developing Cleft Palates

This study shows that all-trans retinoic acid disrupts MEPM cell pluripotency and osteogenic differentiation via miR-106a-5p targeting PTEN, leading to cleft palate development.

Radiologic Evaluation of the Influence of Cleft Type on Nasal Dorsum Growth

The paper evaluates how cleft type affects nasal dorsum growth, finding that cleft lip only (CL) leads to shorter nasal length, while cleft lip with palate (CL/P) results in reduced nasal height and saddle-nose deformity.

Requirement of Irf6 and Esrp1/2 in frontonasal and palatal epithelium to regulate craniofacial and palate morphogenesis in mouse and zebrafish

This study investigates the role of Irf6 and Esrp1/2 in craniofacial development across mouse and zebrafish, identifying their expression patterns and genetic interactions in cleft formation.

Coding de novo mutations identified by WGS reveal novel orofacial cleft genes

The paper identifies coding de novo mutations in whole-genome sequencing data from OFC cases and finds enrichment in genes expressed in craniofacial tissues and linked to OFC syndromes.

Novel truncating mutations in CTNND1 cause a dominant craniofacial and cardiac syndrome

The paper identifies novel truncating mutations in CTNND1 associated with craniofacial and cardiac anomalies, expanding the known phenotypic spectrum of the gene.

Cleft lip/palate and educational attainment: cause, consequence, or correlation? A Mendelian randomization study

This study investigates whether genetic liability to non-syndromic cleft lip/palate influences educational attainment and intelligence, finding little evidence of shared genetic causation.

Analysis of zebrafish periderm enhancers facilitates identification of a regulatory variant near human KRT8/18

The paper identifies a regulatory variant near human KRT8/18 by analyzing zebrafish periderm enhancers and predicting the effect of OFC-associated SNPs.

Cleft lip and cleft palate (CL/P) in Esrp1 KO mice is associated with alterations in Wnt signaling and epithelial-mesenchymal crosstalk

The paper investigates the role of Esrp1 in cleft lip and palate development in mice, identifying altered Wnt signaling and epithelial-mesenchymal interactions as key factors.

Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21

This study uses whole genome sequencing of OFC trios to identify a new locus on chromosome 21 associated with OFCs in Colombian families.

"mir152 hypomethylation, potentially triggered by embryonic hypoxia, as a mechanism for non-syndromic cleft lip/palate"

The paper identifies mir152 hypomethylation as a potential mechanism for non-syndromic cleft lip/palate, linked to embryonic hypoxia in zebrafish models.

Nubp2 is required for cranial neural crest survival in the mouse.

The paper identifies a mutation in Nubp2 through an ENU screen and shows it is required for cranial neural crest survival and midfacial development.

Glycosylphosphatidylinositol Biosynthesis and Remodeling are Required for Neural Crest Cell, Cardiac and Neural Development.

This study identifies a mouse mutant with a mutation in Pgap2, leading to reduced GPI surface expression and developmental defects, and shows folinic acid can rescue some phenotypes.

A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals

The paper develops a framework to analyze subtype-specific and shared genetic effects in orofacial clefting and applies it to identify loci associated with different subtypes.

Anterior Cleft Palate due to Cbfb deficiency and its rescue by folic acid

The paper shows that Cbfb is essential for anterior palatogenesis and that folic acid rescues cleft palate by restoring Stat3 phosphorylation and Tgfb3 expression in vitro.

Accumulation of Rare Coding Variants in Genes Implicated in Risk of Human Cleft Lip with or without Cleft Palate

The paper identifies rare coding variants in genes associated with cleft lip with or without cleft palate by sequencing 49 candidate genes in cases and controls, finding higher variant burdens in cases.

DNA methylation mediates genetic liability to non-syndromic cleft lip/palate

The paper identifies three loci where genetic liability to non-syndromic cleft lip/palate may be mediated by DNA methylation variation in blood and tissue.

Diagnostic outcomes of exome gene panel sequencing in patients with unusual syndromic cleft lip/palate phenotypes

The paper uses exome gene panel sequencing to diagnose syndromic cleft lip/palate patients, finding novel variants in five genes in 36% of cases and highlighting challenges in variant detection due to variable read depth.

Genome Wide Interaction Studies Identify Sex-Specific Risk Alleles for Nonsyndromic Orofacial Clefts

The paper identifies sex-specific risk alleles for nonsyndromic orofacial clefts through genome-wide interaction studies, finding a significant gene-by-sex effect at the 10q21 locus.

Investigating the shared genetics of non-syndromic cleft lip/palate and facial morphology

The paper investigates genetic overlap between non-syndromic cleft lip/palate and facial morphology using polygenic risk scores and Mendelian randomization, finding a causal relationship with philtrum width.

High Resolution Epigenomic Atlas of Early Human Craniofacial Development

The paper creates an epigenomic atlas of early human craniofacial development, identifies novel enhancers, and links them to HOXA genes involved in craniofacial abnormalities.