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Abstract Non-syndromic orofacial clefts (NSOFCs) are common birth defects with a complex etiology. While over 60 common risk loci have been identified, they explain only a small proportion of the heritability for NSOFCs. Rare variants have been implicated in the missing heritability. Thus, our study aimed to identify genes enriched with nonsynonymous rare coding variants associated with NSOFCs. Our sample included 814 non-syndromic cleft lip with or without palate (NSCL/P), 205 non-syndromic cleft palate only (NSCPO), and 2150 unrelated control children from Nigeria, Ghana, and Ethiopia. We conducted a gene-based analysis separately for each phenotype using three rare-variants collapsing models: (1) protein-altering (PA), (2) missense variants only (MO); and (3) loss of function variants only (LOFO). Subsequently, we utilized relevant transcriptomics data to evaluate associated gene expression and examined their mutation constraint using the gnomeAD database. In total, 13 genes showed suggestive associations (p = E−04). Among them, eight genes (ABCB1, ALKBH8, CENPF, CSAD, EXPH5, PDZD8, SLC16A9, and TTC28) were consistently expressed in relevant mouse and human craniofacial tissues during the formation of the face, and three genes (ABCB1, TTC28, and PDZD8) showed statistically significant mutation constraint. These findings underscore the role of rare variants in identifying candidate genes for NSOFCs.

Abstract Background A fundamental ethical issue in African genomics research is how socio-cultural factors impact perspectives, acceptance, and utility of genomic information, especially in stigmatizing conditions like orofacial clefts (OFCs). Previous research has shown that gatekeepers (e.g., religious, political, family or community leaders) wield considerable influence on the decision-making capabilities of their members, including health issues. Thus, their perspectives can inform the design of engagement strategies and increase exposure to the benefits of genomics testing/research. This is especially important for Africans underrepresented in genomic research. Our study aims to investigate the perspectives of gatekeepers concerning genomic risk information (GRI) in the presence of OFCs in a sub-Saharan African cohort. Methods Twenty-five focus group discussions (FGDs) consisting of 214 gatekeepers (religious, community, ethnic leaders, and traditional birth attendants) in Lagos, Nigeria, explored the opinions of participants on genomic risk information (GRI), OFC experience, and the possibility of involvement in collaborative decision-making in Lagos, Nigeria. Transcripts generated from audio recordings were coded and analyzed in NVivo using thematic analysis. Results Three main themes—knowledge, beliefs, and willingness to act—emerged from exploring the perspective of gatekeepers about GRI in this group. We observed mixed opinions regarding the acceptance of GRI. Many participants believed their role is to guide and support members when they receive results; this is based on the level of trust their members have in them. However, participants felt they would need to be trained by medical experts to do this. Also, religious and cultural beliefs were crucial to determining participants’ understanding of OFCs and the acceptance and utilization of GRI. Conclusions Incorporating cultural sensitivity into public engagement could help develop appropriate strategies to manage conflicting ideologies surrounding genomic information in African communities. This will allow for more widespread access to the advances in genomics research in underrepresented populations. We also recommend a synergistic relationship between community health specialists/scientists, and community leaders, including spiritual providers to better understand and utilize GRI.

Abstract Background and objectives One of the major drivers of the novel coronavirus (SARS‐CoV‐2) pandemic is community transmission. Nigeria, like other countries globally, took to strict preventive public health measures including good respiratory and hand hygiene, physical distancing, and the use of face mask to control the spread of COVID-19 disease. Furthermore, the government of Lagos State in Nigeria made a pronouncement on the universal use of face mask in the community. While the use of face masks has proven to be an effective barrier to the transmission of respiratory diseases, its use in the community is uncommon. This study assessed the willingness and compliance with wearing face masks for the reduction of the community spread of COVID-19 and identified possible barriers to use of mask among residents in Lagos State. Methods This was a descriptive cross-sectional study, that surveyed 552 respondents who were adult residents of Lagos State. Data collection was quantitative, using a pretested, interviewer-administered questionnaire, and findings were presented in frequencies and percentages. Pearson’s chi-square and logistic regression analyses were used to test the association between variables. The level of significance was set at 5%. Results A majority (75.7%) of the respondents were willing to wear a face mask in public areas but only 21.9% of the respondents were willing to wear a mask at all times. The most identified barriers to wearing mask were discomfort (72.5%) and inconvenience (77.7%). Two-thirds of the respondents reported they were compliant with always wearing a face mask when leaving home. Only 15.0% of the respondents wore the mask continuously and appropriately, covering the nose and mouth. Having a post-secondary education and being older (40 years and above) were found to be positive predictors of both willingness to wear a mask and compliance with universal mask policy (wearing masks continuously and appropriately). Conclusion Our findings suggest that willingness to wear a face mask influences compliance, and that having a post-secondary education and being older (> 40 years) were positive predictors of both willingness to wear a mask and compliance with universal mask policy (wearing it continuously and correctly). The major barriers to wearing masks were discomfort and inconvenience. Effective risk communication strategies to reach diverse groups for better compliance with public health measures are urgently needed even for the future.

Abstract Introduction The frequency and implications of secondary findings (SFs) from genomic testing data have been extensively researched. However, little is known about the frequency or reporting of SFs in Africans, who are underrepresented in large‐scale population genomic studies. The availability of data from the first whole‐genome sequencing for orofacial clefts in an African population motivated this investigation. Methods In total, 130 case‐parent trios were analyzed for SFs within the ACMG SFv.3.0 list genes. Additionally, we filtered for four more genes (HBB, HSD32B, G6PD and ACADM). Results We identified 246 unique variants in 55 genes; five variants in four genes were classified as pathogenic or likely pathogenic (P/LP). The P/LP variants were seen in 2.3% (9/390) of the subjects, a frequency higher than ~1% reported for diverse ethnicities. On the ACMG list, pathogenic variants were observed in PRKAG (p. Glu183Lys). Variants in the PALB2 (p. Glu159Ter), RYR1 (p. Arg2163Leu) and LDLR (p. Asn564Ser) genes were predicted to be LP. Conclusion This study provides information on the frequency and pathogenicity of SFs in an African cohort. Early risk detection will help reduce disease burden and contribute to efforts to increase knowledge of the distribution and impact of actionable genomic variants in diverse populations.

Abstract 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.

Abstract 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

BackgroundSeveral population-based case-control studies have reported concurrent presentation of cancer and congenital malformations. Many associations have been made between oral clefting and cancers, though some of these results are conflicting. Some studies have reported an increased risk of cancer among 1st-degree relatives of cleft cases and vice versa, and also an excess risk of cancers of the breast, lung, and brain among those with oral clefts. This study aimed to determine if the genetic polymorphisms found in some cancers are also associated with orofacial cleft in an African cohort.MethodsThe study was a case-control and case-triad study in which cases were 400 individuals clinically diagnosed with non-syndromic cleft lip and/or palate (CL/P), while controls were 450 individuals without CL/P. Samples were obtained from three African countries while DNA extraction, PCR, and genotyping were carried out at the University of Iowa, US. Eleven SNPs in genes coding for SWI/SNF subunits and 13 GWAS significant SNPs for cancers associated with orofacial cleft were selected. Case-control analysis, transmission disequilibrium test (TDT), and DFAM to combine the parent-offspring trio data and unrelated case/control data in a single analysis were carried out using PLINK.ResultsFor the case-control analyses that included all the clefts and for the CLP subtype, none of the SNPs were statistically significant. Statistically increased risk for the following SNPs rs34775372 (p = 0.02; OR = 1.54, CI:1.07–2.22), rs55658222 (p = 0.009; OR = 2.64, CI:1.28–5.45) and rs72728755 (p = 0.02; OR=2.27, CI:1.17–4.45) was observed with the CL only sub-group. None of these were significant after Bonferoni correction. In the TDT analyses, a significantly reduced risk with rs10941679 (p = 0.003; OR = 0.43, CI:0.24–0.75) was observed and this was significant after Bonferroni correction. The rs10941679 was also significant (p = 0.003) in the DFAM analyses as well even after Bonferroni correction.ConclusionThe results from this study represent an important starting point for understanding the concurrent presentation of some cancers in orofacial clefts, and cancer risks in cleft patients. The associations observed warrant further investigation in a larger cohort and will set the stage for a more mechanistic approach toward understanding the risk for cancers in families with clefts.

Orofacial clefts (OFCs) are among the most prevalent craniofacial birth defects worldwide and create a significant public health burden. The majority of OFCs are non-syndromic and vary in prevalence by ethnicity. Africans have the lowest prevalence of OFCs (~ 1/2,500), Asians have the highest prevalence (~1/500), Europeans and Latin Americans lie somewhere in the middle (~1/800 and 1/900, respectively). Thus, ethnicity appears to be a major determinant of the risk of developing OFC. The Pittsburgh Orofacial Clefts Multiethnic study was designed to explore this ethnic variance, comprising a large number of families and individuals (~12,000 individuals) from multiple populations worldwide: US and Europe, Asians, mixed Native American/Caucasians, and Africans. In this current study, we analyzed 2,915 OFC cases, 6,044 unaffected individuals related to the OFC cases, and 2,685 controls with no personal or family history of OFC. Participants were grouped by their ancestry into African, Asian, European, and Central and South American subsets, and genome-wide association run on the combined sample as well as the four ancestry-based groups. We observed 22 associations to cleft lip with or without cleft palate at 18 distinct loci with p-values < 1e-06, including 10 with genome-wide significance (

Abstract 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.

Objective: To report the experience of wrong-site tooth extraction among Nigerian dentists. Study design: A self-administered questionnaire was distributed among a cross-section of Nigerian dentists. Information requested included personal experience on wrong-site tooth/teeth extraction and its after-effect, possible reasons for wrong-site tooth extraction and documentation of the event in patients’ case. Respondents were also asked if they were aware of any colleagues who had previously experienced wrong-site tooth extraction and possible legal implication of the event, and if they aware of the universal protocol for preventing wrong site, wrong procedure, and wrong person surgery. Results: Twenty-two (13%) of the respondents reported having extracted a wrong tooth. The event occurred within 5 years after graduation in most cases. Most respondents (53.6%) informed the patient immediately after the event. Only 68% of the respondents documented the event in patient’s case record. Most common reasons for wrong-site tooth extraction were heavy workload, presence of multiple condemned teeth and miscommunication between dentists. Fifty-five percent of respondents were aware of a colleague who had extracted a wrong tooth. The most probable legal implication of wrong-site tooth extraction according to the respondents was litigation by the patient. Only 25% of dentists were aware of a universal protocol for preventing wrong-site surgery. Conclusions: Wrong tooth/teeth extraction is not an uncommon event in the studied environment. The need to be familiar with universal protocol on wrong-site surgery and its legal implications are highlighted. Keywords: Wrong-site, Tooth, Extraction, Dentists

Aim: The study aims to determine the frequency of homologous blood transfusion in patientsundergoing cleft lip and palate surgery at the Lagos University Teaching Hospital, Nigeria. Setting and Design: A prospective study of transfusion rate in cleft surgery conducted at the Lagos University Teaching Hospital, Nigeria. Material and Methods: One hundred consecutive patients who required cleft lip and palate surgery were recruited into the study. Data collected included age, sex and weight of patients, type of cleft defects, type of surgery done, preoperative haematocrit, duration of surgery, amount of blood loss during surgery, the number of units of blood cross-matched and those used. Each patient was made to donate a unit of homologous blood prior to surgery. Results: There were 52 females and 48 males with a mean age of 64.4 ± 101.1 months (range, 3-420 months). The most common cleft defect was isolated cleft palate (45%) followed by unilateral cleft lip (28%). Cleft palate repair was the most common procedure (45%) followed by unilateral cleft lip repair (41%). The mean estimated blood loss was 95.8 ± 144.9 ml (range, 2-800ml). Ten (10%) patients (CL=2; CP=5, BCL=1; CLP=2) were transfused but only two of these were deemed appropriate based on percentage blood volume loss. The mean blood transfused was 131.5 ± 135.4ml (range, 35-500ml). Six (60%) of those transfused had a preoperative PCV of < 30%. Only 4.9% of patients who had unilateral cleft lip surgery were transfused as compared with 50% for CLP surgery, 11% for CP surgery, and 10% for bilateral cleft lip surgery. Conclusions: The frequency of blood transfusion in cleft lip and palate surgery was 10% with a cross-match: transfusion ratio of 10 and transfusion index of 0.1. A “type and screen” policy is advocated for cleft lip and palate surgery.

Background: To curb the spread of the coronavirus disease 2019 (COVID-19), several guidelines for dental practice were proposed by dental practice regulating bodies. Assessing the level of compliance to these guidelines by dental personnel will provide an evidence-based report of their adherence to COVID-19 guidance and if improvement on this is required. Aim: To assess the risk of exposure of dental personnel to COVID-19 in the dental facility and their level of compliance with COVID-19 guidance for the dental practice. Methodology: This was a descriptive cross-sectional study conducted at the Dental Centre of the Lagos University Teaching Hospital, (LUTH) Lagos, Nigeria. Participants were dental personnel (resident doctors/house officers, dental nurses, dental hygienists and dental technologists) at the Dental Centre, LUTH. COVID-19 risk assessment and compliance with COVID-19 dental practice guidance were assessed using a self-administered questionnaire. Results: A total of 131 dental personnel aged 29.4 ± 5.16 years participated in this study. High risk of COVID-19 exposure was noted in trainees in conservative dentistry, paediatric dentistry, oral and maxillofacial surgery, and in dental hygienists. Eight dental personnel (6.1%) reported a confirmed diagnosis of COVID-19. Majority of included specialties reported a low (50%–

Objective: This study was conducted to determine the changes in the blood pressure (BP) and the pulse rate (PR) of normotensive patients having dental extraction under the administration of 2% lignocaine local anesthetic with or without adrenaline. Materials and Methods: This prospective study was carried out on 325 consecutive normotensive patients who presented at the exodontia clinic of the Lagos University Teaching Hospital (LUTH), Lagos, Yoruba State, Nigeria from December 2004 to August 2005 for simple tooth extraction. The patients were randomly allocated into two groups according to the type of anesthetic solution employed. Group A had tooth extraction done under the administration of 2% lignocaine with adrenaline (1:80,000) while group B had tooth extraction done under the administration of 2% lignocaine local anesthetic without vasoconstrictor (plain lignocaine). Each patient had single tooth extracted. The following parameters were monitored in each of the surgical interventions: systolic blood pressure (SBP), diastolic blood pressure (DBP), and PR. Measurements were taken in the waiting room before surgery, during the surgery after local anesthesia, during tooth extraction, and 15 min after tooth extraction. Results: The sample consisted of 176 females and 149 males. Age range of the patients was 18-89 years with the mean age of 35.08 ± 15.60 years. The hemodynamic responses to lignocaine with adrenaline (1:80,000) and plain lignocaine essentially follow the same pattern in the study. There was no statistically significant difference between the measured parameters in the two groups after the administration of local anesthetics. Conclusion: This study, therefore, shows that there was no difference in the hemodynamic changes observed with the use of lignocaine with adrenaline or plain lignocaine during a simple tooth extraction in healthy adults.

Background: Van der Woude syndrome (VWS), an autosomal dominant condition associated with clefts of the lip and/or palate and lower lip pits and is caused by mutations in interferon regulatory factor six gene. It is reported to be the most common syndromic cleft world-wide. Non-penetrance for the lip pit phenotype is found in at least 10% of affected individuals and those without the pits are phenocopies for non-syndromic clefting. The aim of this study is to present the phenotypic characteristic of VWS seen at the Lagos University Teaching Hospital (LUTH) cleft clinic. Materials and Methods: A review of cases of patients with VWS that attended the cleft lip and palate clinic at the LUTH Idi-Araba, Lagos, from January 2007 to December 2012 was conducted. Data analyses included sex of affected patients, types of cleft, presence of lower lip pits and history of lower lip pits/cleft in the family. Results: A total of 11 cases were seen during the period (male = 4; female = 7). Age at presentation ranged between 1 week and 12 years, with majority (n = 10) less than 2 years of age. Bilateral cleft lip and palate (BCLP) was seen in six patients, isolated soft palatal cleft (n = 3) and unilateral cleft lip and alveolus (n = 1) and cleft of hard and soft palate (n = 1). Bilateral lower lips were presented in 10 out of the 11 cases. The mother of the only patient without lip pits presented with bilateral lower lip pits. No family history of cleft/lip pits was elicited in 10 other cases. Conclusion: Most of the cases of VWS presented with BCLP and lower lip pits. Non-penetrance for the lip pits was seen in one out of 11 cases. Our study emphasizes the need to screen family members in all cleft cases, especially clinically diagnosed non-syndromic cases who may be VWS with no lip pits. Future studies are required to investigate the genetic causes of this syndrome in our population.

Aim: The study was designed to explore the changes in oral health-related quality of life (QoL) in the immediate postoperative period following routine (non-surgical) dental extraction. Setting and Design: A prospective study carried out at the Oral and Maxillofacial Surgery clinic of the Lagos University Teaching Hospital, Nigeria. Materials and Methods: Subjects attending who required non-surgical removal of one or two teeth under local anesthesia were included in the study. A baseline QoL questionnaire (oral health impact profile-14 [OHIP-14]) was filled by each patient just before surgery, and only those who were considered to have their QoL "not affected" (total score 14 or less) were included in the study. After the extraction, each subject was given a modified form of "health related QoL" [OHIP-14]-instrument to be completed by the 3 rd day-after surgery, and were given the opportunity to review the questionnaire on the 7 th day postoperative review. Results: Total OHIP-14 scores ranged between 14 and 48 (mean ± SD, 26.2 ± 8.3). Majority of the subjects (60%) reported, "a little affected." Only few subjects (5.8%) reported, "not at all affected," and about 32% reported, "quite a lot." Summation of OHIP-14 scores revealed that QoL was "affected" in 41 subjects (34.2%) and "not affected" in 79 subjects (65.8%). More than 30% of subjects reported that their ability to chew, ability to open the mouth and enjoyment of food were affected following tooth extraction. Few subjects (14-34%) reported deterioration in their speech and less than 20% of subjects reported that change in their appearance was "affected." Only few subjects (12.5-15.1%) reported sleep and duty impairment. Thirty-percent of subjects reported their inability to keep social activities, and 41% were not able to continue with their favorite sports and hobbies. Multiple regression analysis revealed no significant association between age, sex, indications for extraction, duration of extraction, intra-operative complications, and deterioration in QoL ( P < 0.05). Consumption of analgesics beyond postoperative day 1 (POD1) was more common in subjects with socket healing complications than those without ( P = 0.000). About 33% of subjects reported, "inability to work" (1-3 days). Conclusion: About a third of subjects experienced significant deterioration in QoL. The most affected domains were eating/diet variation and speech variation. Therefore, patients should be informed of possible deterioration in their QoL following non-surgical tooth extraction.

The aim of this paper is to review the literature and identify orofacial manifestations of hematological diseases with special reference to hemato-oncologic, immuno-deficiency disorders, and human immunodeficiency virus infection. A computerized literature search using MEDLINE was conducted for published articles on orofacial manifestations of hematological diseases with emphasis on hemato-oncologic and human immunodeficiency virus (HIV) infection. Mesh phrases used in the search were: Oral diseases AND hematological disorders; orofacial diseases AND leukemias; orofacial lesions AND lymphomas; orofacial diseases AND multiple myeloma, orofacial manifestations AND HIV. The Boolean operator "AND" was used to combine and narrow the searches. The full texts of these articles were thoroughly examined. References in these articles also were manually searched non-Medline articles. Only relevant articles were selected for the review. Orofacial manifestation of malignant hematological diseases may present as primary clinical features due to infiltration of orofacial tissues, or as secondary due to the subsequent infiltration of normal bone marrow elements, or tertiary due to the side effects of the treatment. HIV-associated orofacial lesion may be a clinical indicator of HIV infection in otherwise healthy, undiagnosed individuals; an early clinical feature of HIV infection; clinical markers for the classification and staging of HIV disease or may be a predictor of HIV disease progression. Orofacial manifestations of malignant hematological diseases and HIV infection are not uncommon findings in clinical practice. These manifestations may be clinical indicators of hematologic disorders in otherwise healthy, undiagnosed individuals.

The aim of this paper is to review the literature and identify orofacial manifestations of hematological diseases, with particular reference to anemias and disorders of hemostasis. A computerized literature search using MEDLINE was conducted for published articles on orofacial manifestations of hematological diseases, with emphasis on anemia. Mesh phrases used in the search were: oral diseases AND anaemia; orofacial diseases AND anaemia; orofacial lesions AND anaemia; orofacial manifestations AND disorders of haemostasis. The Boolean operator "AND" was used to combine and narrow the searches. Anemic disorders associated with orofacial signs and symptoms include iron deficiency anemia, Plummer-Vinson syndrome, megaloblastic anemia, sickle cell anemia, thalassaemia and aplastic anemia. The manifestations include conjunctiva and facial pallor, atrophic glossitis, angular stomatitis, dysphagia, magenta tongue, midfacial overgrowth, osteoclerosis, osteomyelitis and paraesthesia/anesthesia of the mental nerve. Orofacial petechiae, conjunctivae hemorrhage, nose-bleeding, spontaneous and post-traumatic gingival hemorrhage and prolonged post-extraction bleeding are common orofacial manifestations of inherited hemostatic disorders such as von Willebrand′s disease and hemophilia. A wide array of anemic and hemostatic disorders encountered in internal medicine has manifestations in the oral cavity and the facial region. Most of these manifestations are non-specific, but should alert the hematologist and the dental surgeon to the possibilities of a concurrent disease of hemopoiesis or hemostasis or a latent one that may subsequently manifest itself.