Search

Objectives: This study aims to determine the diagnostic test accuracy (DTA) of hypermethylated DNA biomarkers in saliva and oral swabs for oral squamous cell carcinoma (OSCC) detection from the prevalidation studies available. Materials and Methods: Electronic database searching of PubMed, EMBASE, Cochrane Library, Scopus, Web of Science, and LILACS was conducted to identify relevant articles that were published between January 1, 2000, and August 1, 2020. Results: Meta-analysis was conducted based on 11 of 20 studies selected for review. Included studies had high bias concerns on the QUADAS-2 study assessment tool. We found that salivary and oral swab hypermethylation markers had better specificity than sensitivity for oral cancer detection. Summary sensitivity and specificity (95% CI) of hypermethylation panels were 86.2% (60–96.2) and 90.6% (85.9–93.9) while for individual markers, summary sensitivity and specificity (95% CI) were 70% (56.9–80.5) and 91.9% (80.3–96.9), respectively. Respective positive and negative likelihood ratios for combined markers were 9.2 (5.89–14.36) and 0.15 (0.05–0.5), and 8.61 (3.39–21.87) and 0.33 (0.22–0.49) for single-application biomarkers. Conclusion: DNA hypermethylation biomarkers especially in combination have acceptable DTA that warrants further optimization with rigorous biomarker evaluation methods for conclusive determination of their efficacy.

BACKGROUND: Van der Woude syndrome (VWS) is the most common syndromic orofacial cleft which accounts for approximately 2% of all cleft lip (CL) and/or palate cases. It is characterized by the presence of lower lip pits, in addition to CL, CL with or without cleft palate, cleft palate only, and hypodontia. It is inherited as an autosomal-dominant trait with almost complete penetrance but variable expressivity, and different variants in IRF6 gene have been reported in different populations around the world including African populations (Ethiopian, Ghanaian, and Nigerian). METHODS AND FINDINGS: The authors investigated the role of IRF6 in Ethiopian families with VWS. The DNA of 7 families with VWS from Ethiopia were screened by Sanger sequencing. The authors screened all 9 exons of IRF6 and found a novel missense variant in exon 4 (p. Gly65Glu). This variant was predicted to be deleterious/probably damaging by Sift and PolyPhen, respectively. The IRF6 variant (p. Gly65Glu) segregates in the family since it was identified in the father and a sibling. CONCLUSION: Several of the individuals with lower lip pits in this study did not seek treatment. This is due to lack of awareness about the significance of this minor looking deformity and its consequences, and availability of treatment for birth defects. Therefore, it is important to educate families. Finally, screening for novel variants in known genes has a role in counseling and prenatal diagnosis for high-risk families.

Introduction: Malnutrition in children is one of the most prevalent global health challenges, and malnourished children have a higher risk of death from childhood diseases. Early childhood caries (ECC) is the most common chronic disease of childhood. Complications from ECC such as pain, loss of tooth/teeth, and infection can undermine a child’s nutrition and growth. Aim: This study aims to evaluate the severity of decay, missing, and filled tooth (dmft) by nutritional status using the z scores of the anthropometric measurements: height for age (HFA), weight for age (WFA), weight for height (WFH), and body mass index for age (BMIA) among children with ECC in Nigeria. Study Design: This is a cross-sectional study conducted in 5 local government areas (LGAs) in Lagos State, Nigeria. A multistage sampling technique was used. Results: A total of 273 cases of ECC were included in the analyses (mean age 4.19 ± 0.96 y). Overall, the mean dmft was 3.04 ± 2.28, and most (96%) were accounted for by untreated decay. The distribution of dmft within the different z score categories of BMIA (+3 = obese) showed the highest dmft scores among the combined severely wasted and wasted groups, lowest among children with normal z scores, and intermediate in the overweight and obese groups. There was a significant negative correlation between BMIA z score, WFH z score, and dmft ( r = −0.181, P < 0.05 and r = −0.143, P < 0.05, respectively). However, the correlations between HFA z score, WFA z score, and dmft were positive but not significant ( r = 0.048, P = 0.44 and r = 0.022, P = 0.77, respectively). Conclusion: Our study showed an increased severity of dental caries among severely wasted or wasted children with ECC compared to those of normal or overweight. Knowledge Transfer Statement: The results from this study will raise awareness among clinicians and policy makers on the need for a primary prevention program for early childhood caries in countries with high burden of malnutrition and limited resources. Also, it will help draw the attention of clinicians to the caries status of malnourished children that can be managed to improve the nutritional outcomes.

Background Orofacial clefts (OFCs) are congenital malformations of the face and palate, with an incidence of 1 per 700 live births. Clubfoot or congenital talipes equinovarus (CTEV) is a three‐dimensional abnormality of the leg, ankle, and feet that leads to the anomalous positioning of foot and ankle joints and has an incidence of 1 per 1000 live births. OFCs and CTEV may occur together or separately in certain genetic syndromes in addition to other congenital abnormalities. Here, we sought to decipher the genetic etiology of OFC and CTEV that occurred together in six probands. Methods At the time of recruitment, the most clinically obvious congenital anomalies in these individuals were the OFC and CTEV. We carried out whole‐exome sequencing (WES) on DNA samples from probands and available parents employing the Agilent SureSelect XT kit and Illumina HiSeq2500 platform, followed by bioinformatics analyses. WES variants were validated by clinical Sanger Sequencing. Results Of the six probands, we observed probable pathogenic genetic variants in four. In three probands with probable pathogenic genetic variants, each individual had variants in three different genes, whereas one proband had probable pathogenic variant in just one gene. In one proband, we observed variants in DIS3L2, a gene associated with Perlman syndrome. A second proband had variants in EPG5 (associated with Vici Syndrome), BARX1 and MKI67, while another proband had potentially etiologic variants in FRAS1 (associated with Fraser Syndrome 1), TCOF1 (associated with Treacher Collins Syndrome 1) and MKI67. The last proband had variants in FRAS1, PRDM16 (associated with Cardiomyopathy, dilated, 1LL/Left ventricular noncompaction 8) and CHD7 (associated with CHARGE syndrome/Hypogonadotropic hypogonadism 5 with or without anosmia). Conclusion Our results suggest that clubfoot and OFCs are two congenital abnormalities that can co‐occur in certain individuals with varying genetic causes and expressivity, warranting the need for deep phenotyping., Whole‐exome sequencing was applied to hunt for possible etiologic variants in six individuals that presented with orofacial clefts and clubfoot. Our genomics and bioinformatics analyses revealed many genetic syndromes in four out of the six probands, with multiple variants in genes associated with certain genetic syndromes being observed in some probands.

Background Early childhood caries (ECC) is a rapidly progressing form of dental infection and a significant public health problem, especially among socially and economically disadvantaged populations. This study aimed to assess the risk factors for ECC among a cohort of Sub-Saharan African children and to determine the role of genetics in the etiology of ECC. Methods A sample of 691 children (338 with ECC, 353 without ECC, age Results Of the 338 children with ECC, 64 (18.9%) had Severe-Early Childhood Caries (S-ECC). Children aged 48–59 months comprised the highest proportion of subjects with ECC (165; 48.8%) and S-ECC (24; 37.5%) while female subjects had higher dt (3.13 ± 2.56) and dmft values 3.27 ± 2.64. ECC was significantly more prevalent among children who were breastfed at night ≥ 12 months (OR 3.30; CI 0.39, 4.75), those with no previous dental visit (OR 1.71; CI 0.24, 2.77), those who used sweetened pacifiers (OR 1.85; CI 0.91, 3.79) and those who daily consumed sugar-sweetened drinks/snacks (OR 1.35; CI 0.09, 18.51). A suggestive increased risk for ECC (OR 1.26, p = 0. 0.0397) was observed for the genetic variant rs11239282 on chromosome 10. We also observed a suggestive reduced risk for ECC (OR 0.80, p = 0.03) for the rs131777 on chromosome 22. None of the genetic variants were significant after correction for multiple testing (Bonferroni p value p = 0.004). Conclusions Prolonged night-time breastfeeding, poor utilization of dental services and daily consumption of sugar were risk factors for ECC. Larger sample size is needed to confirm the results of the genetic analysis and to conduct genome wide studies in order to discover new risk loci for ECC.

Background The development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well‐organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA‐binding (exon 3, 4) or protein‐binding domains (exon 7–9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico. Methods We used PubMed with the search terms; "Van der Woude syndrome," “Popliteal pterygium syndrome,” "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants. Results Twenty‐one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7–9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein‐binding domain (exon 7–9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*). Conclusion Mutations in the protein and DNA‐binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes., The study reported novel variants in IRF6 from patients with VWS. Updated the list of all IRF6 variants reported from 2013 to date and provide an insight into on how to use the Combined Annotation Dependent Depletion score for the prioritization of IRF6 variants.