Genomic analyses in African populations identify novel risk loci for cleft palate.

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

A Genome-wide Association Study of Nonsyndromic Cleft Palate Identifies an Etiologic Missense Variant in GRHL3.

Cleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met [c.1361C>T]; rs41268753; p = 4.08 × 10(-9)) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR = 8.3, 95% CI 4.1-16.8; OR = 2.16, 95% CI 1.43-3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis.

A multi-ethnic genome-wide association study identifies novel loci for non-syndromic cleft lip with or without cleft palate on 2p24.2, 17q23 and 19q13.

Orofacial clefts (OFCs), which include non-syndromic cleft lip with or without cleft palate (CL/P), are among the most common birth defects in humans, affecting approximately 1 in 700 newborns. CL/P is phenotypically heterogeneous and has a complex etiology caused by genetic and environmental factors. Previous genome-wide association studies (GWASs) have identified at least 15 risk loci for CL/P. As these loci do not account for all of the genetic variance of CL/P, we hypothesized the existence of additional risk loci. We conducted a multiethnic GWAS in 6480 participants (823 unrelated cases, 1700 unrelated controls and 1319 case-parent trios) with European, Asian, African and Central and South American ancestry. Our GWAS revealed novel associations on 2p24 near FAM49A, a gene of unknown function (P = 4.22 × 10-8), and 19q13 near RHPN2, a gene involved in organizing the actin cytoskeleton (P = 4.17 × 10-8). Other regions reaching genome-wide significance were 1p36 (PAX7), 1p22 (ARHGAP29), 1q32 (IRF6), 8q24 and 17p13 (NTN1), all reported in previous GWASs. Stratification by ancestry group revealed a novel association with a region on 17q23 (P = 2.92 × 10-8) among individuals with European ancestry. This region included several promising candidates including TANC2, an oncogene required for development, and DCAF7, a scaffolding protein required for craniofacial development. In the Central and South American ancestry group, significant associations with loci previously identified in Asian or European ancestry groups reflected their admixed ancestry. In summary, we have identified novel CL/P risk loci and suggest new genes involved in craniofacial development, confirming the highly heterogeneous etiology of OFCs.

Strategies adopted by oral physicians, oral and maxillofacial surgeons, and oral pathologists in patient education on oral cancer: A Nigerian study.

BACKGROUND: The burden of oral cancer in Nigeria is increasing. Different studies have shown how public education on oral cancer have increased knowledge of oral cancer across populations, however, it is not known if these practices are adopted by oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. AIMS: To investigate the patient oral cancer education strategies adopted by oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. METHODS: This study adopted an analytical cross-sectional study design. This study surveyed practicing oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria. An e-questionnaire was used for this study. The data were analyzed using the SPSS Version 20 software, and a p-value of <.05 was used to determine the level of statistical significance. RESULTS: The study's response rate was 46.6% (75/161). The 75 participants were from the six geopolitical zones in Nigeria responded to the survey questionnaire. Even though more than half (43/75, 57.3%) of the respondents have never received any training since their post-bachelor's degree qualification on the strategies that can be used in educating patients on oral cancer, majority (54/75, 72.0%) of them knew at least one education strategy; also, the most known (36/54, 66.7%) and utilized (33/54, 61.3%) strategy among those respondents who were aware of patient education strategy was health talk. Only 38.7% (29/75) of the respondents reported that health learning materials (posters, leaflets, fliers, and flipcharts) are available in their clinics, all of which were in insufficient quantities. Also, 93.3% (70/75) of the respondents opined that it is worthwhile that dental clinics/hospitals in Nigeria invest in the provision of oral cancer learning materials for patient use. Inferential statistical analysis did not reveal any significant relationship between the respondents' characteristics and their awareness and practice on patient oral cancer education strategies. CONCLUSION: This study identified that many oral physicians, oral and maxillofacial surgeons, and oral pathologists in Nigeria lack the needed capacity to educate their patients on oral cancer. There is a need to strengthen their capacity by giving them training on patient oral cancer education strategies, and by providing them with good quality and enough teaching aids.

Applications of yoga in oral oncology: A systematic scoping review.

Background and Aims: Yoga is well-thought-out as an all-inclusive approach globally and can be administered in clinical care as an integrative or alternate approach to regular treatment. Yoga exercise has been disclosed to influence remission from cancer cells over a long period of time and also reverses epigenetic alterations. Applications of Yoga in the management of oral oncology patients are scarce, hence the need for a scoping review of the literature. Hence, this study aimed to conduct a scoping review of the existing empirical evidence on the applications of yoga in oral oncology. Methods: The review methodology was informed by Joanna Brigg's Institute guidelines for systematic scoping reviews, and the review was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews. Ten databases were searched. The records of all the literature retrieved from the search were imported into the Rayyan software for deduplication. After the full-text screening, only two were found eligible for inclusion in the scoping review. Data obtained in the included literature were extracted and synthesized. Results: This review found that Yoga was not significantly effective in the management of stress among oral cancer patients (p-values > 0.04). However, it was found that Yoga significantly reduced anxiety, saliva stickiness, and episodes of falling ill (p-values < 0.05) while it improved mental well-being, cognitive functioning, emotional functioning, and head and neck pain of those oral cancer patients that received it (p-values < 0.05). Conclusion: An integrative care approach that considers nonpharmaceutical techniques such as yoga could help to reduce care cost while improving care outcomes and quality of life of oral cancer patients. Hence, it is imperative to consider yoga along with its potential benefits, and we recommend gradual incorporation of yoga into oral cancer care.

Preventative interventions by dental care professionals in Africa on oral human papillomavirus, gonorrheal, chlamydial, syphilitic and trichomonas infections: A scoping review.

Background: Oral human papillomavirus (HPV), gonorrheal, chlamydial, syphilitic and trichomonas infections are very common sexually transmitted diseases (STDs) in Africa. However, no known study has reviewed the available evidence concerning the preventative interventions by dental care professionals (DCPs) in Africa on oral STDs; hence, this scoping review was conducted to evaluate the research landscape of this topic area in Africa. Methods: The scoping review methodology and documentation were informed by the Arksey and O'Malley's guideline, the Preferred Reporting Items for Systematic Reviews and Meta-analysis extension for conducting Scoping Reviews (PRISMA-ScR) checklist, and the AMSTAR-2 guideline. Ten electronic research databases were searched to retrieve literatures relevant to the scoping review question. The retrieved literature were deduplicated and screened for eligibility based on the review's selection criteria. Data charting, collation and summarization were intended to be done in this review, but it could not be done because no relevant literature was found eligible for inclusion into this scoping review. Results: A total of 523 literature were retrieved. After deduplication of the retrieved literatures, the residual literatures (n = 353) were screened for eligibility for inclusion into the review, of which no eligible article was found. Hence, this scoping review was an empty review. Conclusion: This empty scoping review demonstrates that DCPs in Africa do not engage in research-based oral STD prevention. Therefore, the implementation of research-based preventative interventions, by DCPs, on oral STDs should be encouraged in Africa.

Management of Maxillofacial Gunshot Injuries With Emphasis on Damage Control Surgery During the Yemen Civil War. Review of 173 Victims From a Level 1 Trauma Hospital in Najran, Kingdom of Saudi Arabia.

Study Design: Studies on the concept of Damage Control Surgery (DCS) in the management of firearm injuries to the oral and maxillofacial region are still scarce, hence the basis for the current study. Objectives: The objectives of the current study is to share our experience in the management of maxillofacial gunshot injuries with emphasis on DCS and early definitive surgery. Methods: This was a retrospective study of combatant Yemeni patients with maxillofacial injuries who were transferred across the border from Yemen to Najran, Kingdom of Saudi Arabia. Demographics and etiology of injuries were stored. Paths of entry and exit of the projectiles were also noted. Also recorded were types of gunshot injury and treatment protocols adopted. Data was stored and analyzed using IBM SPSS Statistics for Windows Version 25 (Armonk, NY: IBM Corp). Results: A total of 408 victims, all males, were seen during the study period with 173 (42.4%) males sustaining gunshot injuries to the maxillofacial region. Their ages ranged from 21 to 56 years with mean ± SD (27.5 ± 7.6) years. One hundred and twenty-one (70.0%) victims had extraoral bullet entry, while 53 (30.0%) victims had intraoral entry route. Ocular injuries, consisting of 25 (14.5%) cases of ruptured globe and 6 (3.5%) cases of corneal injuries, were the most commonly associated injuries. A total of 78 (45.1%) hemodynamically unstable victims had DCS as the adopted treatment protocol while early definitive surgery was carried out in 47(27.2%) hemodynamically stable victims. ORIF was the treatment modality used for the fractures in 132 (76.3%) of the victims. Conclusions: We observed that 42.4% of the war victims sustained gunshot injuries. DCS with ORIF was the main treatment protocol adopted in the management of the hemodynamically unstable patients.

Whole-genome sequencing reveals de-novo mutations associated with nonsyndromic cleft lip/palate.

The majority (85%) of nonsyndromic cleft lip with or without cleft palate (nsCL/P) cases occur sporadically, suggesting a role for de novo mutations (DNMs) in the etiology of nsCL/P. To identify high impact protein-altering DNMs that contribute to the risk of nsCL/P, we conducted whole-genome sequencing (WGS) analyses in 130 African case-parent trios (affected probands and unaffected parents). We identified 162 high confidence protein-altering DNMs some of which are based on available evidence, contribute to the risk of nsCL/P. These include novel protein-truncating DNMs in the ACTL6A, ARHGAP10, MINK1, TMEM5 and TTN genes; as well as missense variants in ACAN, DHRS3, DLX6, EPHB2, FKBP10, KMT2D, RECQL4, SEMA3C, SEMA4D, SHH, TP63, and TULP4. Many of these protein-altering DNMs were predicted to be pathogenic. Analysis using mouse transcriptomics data showed that some of these genes are expressed during the development of primary and secondary palate. Gene-set enrichment analysis of the protein-altering DNMs identified palatal development and neural crest migration among the few processes that were significantly enriched. These processes are directly involved in the etiopathogenesis of clefting. The analysis of the coding sequence in the WGS data provides more evidence of the opportunity for novel findings in the African genome.

Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub-Saharan Africa.

Orofacial clefts (OFC) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man (OMIM) database, of which Van der Woude syndrome (VWS) is one of the most common (accounting for 2% of all OFC). Popliteal pterygium syndrome (PPS) is considered to be a more severe form of VWS. Mutations in the IRF6 gene have been reported worldwide to cause VWS and PPS. Here, we report studies of families with VWS and PPS in sub-Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice-site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice-site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF6-related VWS and PPS in sub-Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high-risk families.