Monozygotic (MZ) twins are expected to share nearly identical genomes, yet a substantial proportion is discordant for complex diseases like nonsyndromic orofacial clefts (nsOFC). This suggests a role for postzygotic discordant genetic variations and other developmental mechanisms. In this study, we performed whole genome sequencing of two MZ twin pairs of African ancestry who were discordant for nsOFC to identify genetic variants that may contribute to phenotypic discordance. Following quality control and genotype‐level filtering, we identified 37,271 variants that were present exclusively in the affected twins. Of these, 431 variants were predicted by CADD to have deleterious effects. Among these, 66 were in protein‐coding regions, including 2 predicted protein‐altering missense variants and splice‐site variants. The remaining 365 variants were in noncoding regions including putative craniofacial enhancers. Some of these variants are rare (MAF < 0.01) and were predicted to alter transcription factor binding or disrupt local chromatin architecture within putative craniofacial enhancers located near genes with established roles in craniofacial development, including COL27A1 , MPHOSPH8 , and SPTBN1 . In addition, some common variants previously associated with noncraniofacial traits were also predicted to affect regulatory activity of putative craniofacial enhancers near craniofacial genes. This raises the possibility of pleiotropic regulatory effects that warrant further investigation. Overall, this study identified a set of candidate coding and regulatory variants in MZ twins discordant for nsOFC,providing targets for future functional investigations. We also proposed an overarching genetic mechanism for the prioritized discordant variants.

Periodontitis is a chronic inflammatory disease of the periodontium, affecting nearly 50% of U.S. adults over 30 years old. While dental plaque is the prim

Background: Head and neck tumors pose a major health challenge in Nigeria, yet the factors that influence their severity remain poorly understood. No predictive model currently exists to assess malignancy risk in this population. This study aimed to identify key clinical and demographic predictors and to develop a model for malignancy risk in tumors diagnosed in Lagos, Nigeria. Methods: We analyzed patient records with tumor diagnoses from 2000 to 2024, obtained from the Oral and Maxillofacial Surgery and Oral Pathology departments of the Lagos University Teaching Hospital. Surgical biopsy records and corresponding histopathology reports were reviewed. Tumor sites were grouped into five anatomical regions: mandible, midface, oral mucosa and salivary glands, extra oral, and unspecified regions. Descriptive statistics summarized patient and tumor features, while statistical analyses examined associations between demographics and tumor severity (benign/malignant). A predictive model for tumor severity was developed using data-splitting and leave-one-out cross-validation approaches. Results: Of the 1,068 patients, 1,062 had confirmed diagnoses. Median age was 35 years [IQR:23–52], 53.96% were male, and the mandible was the most common site (48.31%). Tumors were most frequent on the right (30.13%) and measured 6 × 4x2cm on average. Median duration of presentation was 12 months [IQR:5–36], with 50.75% benign tumors. Tumor severity was significantly associated with age (47 vs. 28 years), site, laterality, duration ( p < 0.001), and sex ( p = 0.024), with males more susceptible to malignancy. Age inversely correlated with presentation duration ( p = 0.00067), and tumor site was not associated with sex ( p = 0.054). Conventional ameloblastoma was the most common benign tumor, while squamous cell carcinoma was the most common malignancy. Multivariate analysis showed malignancy was associated with age (OR = 1.61; p < 0.001), tumor site (midface (OR = 3.88), oral mucosa and salivary glands (OR = 23.8), and extraoral sites (OR = 108.01) compared to the mandible [all p < 0.001]), length (OR = 1.93; p < 0.001), and shorter duration (OR = 0.68; p < 0.001). Central (OR = 0.2), left (OR = 0.46), or right laterality (OR = 0.32) lowered malignancy odds versus unspecified (all p < 0.04). Our predictive model approaches achieved area under the curve of 0.864 and 0.883. Conclusions: We identified age, site, laterality, and duration before presentation, as key malignancy predictors. This will aid comprehensive care plans for optimal clinical outcomes.

Van der Woude syndrome (VWS) is the most common syndromic form of orofacial clefts (OFCs). The heritability of VWS is largely (~70%) explained by variants in the IRF6 gene. Experimental studies to confirm genetic variant effects are essential but are time intensive and expensive. Advancing next-generation sequencing techniques has made it possible to identify genetic variation quicker than their causal effects in disease processes can be ascertained. Therefore, employing computational tools to reliably predict their causal effects is crucial for advancing translational research. We conducted Sanger sequencing of the IRF6 gene in 46 VWS cases across 34 families to identify likely causal missense variants. We then assessed structure-informed stability changes to the IRF6 protein when these variants were incorporated into the protein, using DDGun3D. We compared DDGun3D predictions to results from previous experimental studies. Among four variants previously shown to prevent functional rescue in zebrafish, only the variant IRF6(NM_006147.4):c.881T>C, shown to cause rupture of zebrafish embryo, exhibited a high free energy change (∆∆G_fold = 3.5 kcal/mol), indicating that substantial predicted thermodynamic destabilization does not capture all disruptive function of IRF6. Our study demonstrates the utility of a protein structure-based computational approach for functional variant interpretation, providing a complementary method for studying genetic variation. Integrating computational predictions with experimental data can enhance our understanding of genetic conditions. However, success depends on fully elucidating protein structures, which is an active area of research.