Could retaining the dental recall interval save NHS dentistry?

The World Health Assembly in May 2021 was a watershed moment in oral health, with the landmark resolution that designated oral diseases as non-communicable diseases (NCDs). This was strongly supported by a host of other NCDs in recognition of the common risk factor principle and acknowledgement of the fact that oral diseases do not occur in isolation from other NCDs, but are commonly associated with cardiovascular disease, diabetes/obesity, respiratory diseases, metabolic syndrome, a range of other inflammatory disorders and cancers. Regular monitoring and early detection would potentially intercept these NCDs and this could form a central plank of a revamped holistic 'health'- as opposed to 'disease'-oriented health care system.Consultation with patients and dentists reveals strong support for maintaining regular recall intervals, which maintains trust and optimises motivation and compliance. In-person visits could be minimised by using technology, such as remote consultations and longitudinal monitoring systems, making it adaptable to different health care settings and equitable, affordable, cost-effective and sustainable.A new paradigm with dentists as oral health professionals, and the mainstreaming of oral health and population-level prevention, means the future of health care can be guided by integration and workforce modification producing a surveillance-based, early interceptive, preventive model of care.

Shared genetic risk between major orofacial cleft phenotypes in an African population.

Nonsyndromic orofacial clefts (NSOFCs) represent a large proportion (70%-80%) of all OFCs. They can be broadly categorized into nonsyndromic cleft lip with or without cleft palate (NSCL/P) and nonsyndromic cleft palate only (NSCPO). Although NSCL/P and NSCPO are considered etiologically distinct, recent evidence suggests the presence of shared genetic risks. Thus, we investigated the genetic overlap between NSCL/P and NSCPO using African genome-wide association study (GWAS) data on NSOFCs. These data consist of 814 NSCL/P, 205 NSCPO cases, and 2159 unrelated controls. We generated common single-nucleotide variants (SNVs) association summary statistics separately for each phenotype (NSCL/P and NSCPO) under an additive genetic model. Subsequently, we employed the pleiotropic analysis under the composite null (PLACO) method to test for genetic overlap. Our analysis identified two loci with genome-wide significance (rs181737795 [p = 2.58E-08] and rs2221169 [p = 4.5E-08]) and one locus with marginal significance (rs187523265 [p = 5.22E-08]). Using mouse transcriptomics data and information from genetic phenotype databases, we identified MDN1, MAP3k7, KMT2A, ARCN1, and VADC2 as top candidate genes for the associated SNVs. These findings enhance our understanding of genetic variants associated with NSOFCs and identify potential candidate genes for further exploration.

Utilising massive open online courses to enhance global learning dissemination in cleft lip and palate: a case report of penta helix collaboration.

BACKGROUND: Educating and raising awareness in cleft lip and palate future generations is one vital effort to ensure the improvement of cleft care and research in the future. This study reported the overview in organising and evaluating the Massive Open Online Course (MOOC) in Cleft Lip and Palate as the alternative way for students' capacity building outside their study program whilst also earning credits towards their studies. METHODS: Smile Train cleft charity generously donated recorded lectures from cleft experts around the world in which each of the experts agreed to provide one-hour live discussion sessions. The learning activities ranging from lectures, pre- and post-course evaluation, forum, live discussion sessions, virtual visits to Indonesian Cleft Centre, self-reflection assignments and final project. A survey was released to the participants to collect their feedback. RESULTS: The course mainly attracted dental students, and several allied health professional students. In total, 414 out of 717 participants registered for this MOOC managed to finish the course and received a certificate of completion which was run between August-October 2021. In general, participants positively received the course. CONCLUSIONS: The MOOC model and its objective of disseminating widespread information across geographical boundaries to enhance learning about cleft lip and palate treatment was achieved. This report serves as an example for other educational institutions and stakeholders who plan to use online educational engagement platforms to provide high-quality education and capacity building to participants in lower-middle income countries.

Perceptions and beliefs of community gatekeepers about genomic risk information in African cleft research.

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.

Parents and Provider Perspectives on the Return of Genomic Findings for Cleft Families in Africa.

BACKGROUND: Inadequate knowledge among health care providers (HCPs) and parents of affected children limits the understanding and utility of secondary genetic findings (SFs) in under-represented populations in genomics research. SFs arise from deep DNA sequencing done for research or diagnostic purposes and may burden patients and their families despite their potential health importance. This study aims to evaluate the perspective of both groups regarding SFs and their choices in the return of results from genetic testing in the context of orofacial clefts. METHODS: Using an online survey, we evaluated the experiences of 252 HCPs and 197 parents across participating cleft clinics in Ghana and Nigeria toward the return of SFs across several domains. RESULTS: Only 1.6% of the HCPs felt they had an expert understanding of when and how to incorporate genomic medicine into practice, while 50.0% agreed that all SFs should be returned to patients. About 95.4% of parents were willing to receive all the information from genetic testing (including SFs), while the majority cited physicians as their primary information source (64%). CONCLUSIONS: Overall, parents and providers were aware that genetic testing could help in the clinical management of diseases. However, they cited a lack of knowledge about genomic medicine, uncertain clinical utility, and lack of available learning resources as barriers. The knowledge gained from this study will assist with developing guidelines and policies to guide providers on the return of SFs in sub-Saharan Africa and across the continent.

Age at primary surgery among orofacial cleft individuals in Indonesia.

OBJECTIVES: To observe the age at primary cleft surgery among charity organizations such as Smile Train in helping Indonesia manage patients with OFC. MATERIALS AND METHODS: A retrospective analysis of medical records was conducted to identify patients with orofacial clefts who underwent primary surgery between 2001 and 2021. The age at the time of surgery was recorded for each patient. Descriptive statistics were used to analyse the data and determine the average age at primary surgery. RESULTS: In the period between 2001 and 2021, a total of 34 239 individuals in Indonesia underwent primary lip surgery, while 16 768 individuals received primary palatal surgery, as recorded in the Smile Train database. Notably, a significant proportion of these surgeries were classified as delayed primary repairs. Approximately 65.3% of primary lip surgeries were performed beyond the recommended timeline of 6 months of age, indicating a delay in the surgical intervention. Similarly, 67% of primary palatal surgeries were also delayed, occurring after the recommended timeline of 18 months of life. CONCLUSIONS: This study provides insights into the age at primary surgery among individuals with orofacial clefts in Indonesia. The findings highlight the need for timely intervention and the importance of considering individualized treatment plans based on the specific type of orofacial cleft. Further research is warranted to explore factors influencing the age at primary surgery and their impact on treatment outcomes and long-term functional outcomes in this population.

Situational analysis of nutritional status among 1899 children presenting with cleft lip and/or palate in Indonesia.

Background: Given the increased risk of malnutrition in children with cleft lip and/or palate (CLP), determining their nutritional status is critical for preventing adverse surgical risks. However, no such disaggregated, national-level data are available in Indonesia. We aimed to determine the nutritional status of patients with clefts in Indonesia and to identify problems and solutions for malnutrition cases within the population. Methods: In this cross-sectional study, we considered records of individuals who underwent primary surgery for CLP in Smile Train-sponsored facilities in Indonesia between 1 January 2016 and 31 December 2021 (n = 18 480). We only included children under the age of five with an evaluation date prior to admission date and excluded subjects with invalid data values. We classified their nutritional status by z-scores according to the World Health Organization Child Growth Standard (2006). Malnutrition cases cover four indicators - stunting, wasting, underweight, and overweight. We compared the prevalence for malnutrition cases in children under the age of five using national health survey data. Results: We included 1899 records following data validation. The national prevalence of stunting (24.4%), wasting (12.5%), and overweight cases (12.9%) was high, while underweight cases (6.8%) were comparatively low. Statistical analyses showed significant differences in nutritional status based on length/height-for-age between girls and boys aged 0-5 months (P = 0.008) and 48-60 months (P = 0.001), and based on body mass index-for-age (P = 0.000) between girls and boys aged 0-5 months. Girls in different age groups exhibited a statistically significant difference in nutritional status based on length/height-for-age (P = 0.002) and weight-for-age (P = 0.017). Concurrent stunting and overweight were the most common forms of concurrent malnutrition (8.7%). We found a significant difference in the prevalence of underweight (P = 0.001) and overweight (P = 0.000) cases between children with CLP and those without CLP. Conclusions: Our findings highlight the importance of nutritional interventions for children with orofacial clefts in Indonesia, and the importance of age and gender in their design and implementation. Further investigation is necessary to explore the risks of overweight and concurrent malnutrition among this population.

Scoping review of outcome measures in cleft care used in research and reports.

Treatment outcome measures are critical in the decision making of best practices in the OFC field. OFC consortium working groups provided standardization of outcome measures based on previous treatment outcome studies. However, the implementation of such standardization in OFC centres worldwide is unknown. This study presented mapped outcome measures in cleft care using a structured review method complemented by quantitative overview of the relevant published research to provide initial guidelines for the implementation of treatment outcome standardization. A scoping review of the literature of treatment outcomes in cleft care following Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews guidelines was performed. The selected indexed paper in outcome measures mapped following the international consortium in standard set of outcome measures in cleft care. Three hundred and sixty-five articles were filtered. The most discussed domains of cleft care were dental and oral health, appearance and speech/communication. Overall, the majority of publications were produced in high-income countries. The current review indicates that there are inequalities of treatment outcome studies among the domain of cleft care. In addition, there are also inequalities of published articles from HIC versus LMIC in treatment outcomes. This information can be used to develop targeted interventions aimed at encouraging cleft centres worldwide to adapt standardized outcome measures.

Clinically actionable secondary findings in 130 triads from sub-Saharan African families with non-syndromic orofacial clefts.

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.

Global perspectives in orofacial cleft management and research.

Orofacial clefts (OFCs) refer to clefts of the lip and palate, a heterogeneous group of relatively common congenital conditions that can cause mortality and significant disability if untreated, and residual morbidity even when treated with multidisciplinary care. Contemporary challenges in the field include: lack of awareness of OFCs in remote, rural and impoverished populations; uncertainties due to lack of surveillance and data gathering infrastructure; inequitable access to care in some parts of the world; and lack of political will combined with lack of capacity to prioritise research.OFCs present clinically as either syndromic or non-syndromic, with the latter either being isolated or in conjunction with other malformations; however, many registries still do not differentiate between these fundamentally different entities and lump a spectrum of cleft types and sub-phenotypes together. This has implications for treatment, research and ultimately, quality improvement.This paper deals with the challenges in contemporary management in terms of care and the prospects and possibilities for primary prevention of non-syndromic clefts. In terms of management and optimal care, there are also challenges in the provision of multi-disciplinary treatment and management of the consequences of being born with OFCs, such as dental caries, malocclusion and psychosocial adjustment.

Core outcomes for orofacial clefts: reconciling traditional and ICHOM minimum datasets.

OBJECTIVE/DESIGN/SETTING: This retrospective study sought voluntary participation from leading cleft centres from Europe and Brazil regarding core outcome measures. The results of this study would inform the debate on core outcome consensus pertaining to the European Reference Network for rare diseases (ERN CRANIO) and achieve a core outcome set for cleft care providers worldwide. INTERVENTION/METHOD: Five orofacial cleft (OFC) disciplines were identified, within which all of the International Consortium of Health Outcomes Measurement (ICHOM) outcomes fall. One questionnaire was designed for each discipline and comprised 1. the relevant ICHOM's outcomes within that discipline, and 2. a series of questions targeted to clinicians. What core outcomes are currently measured and when, did these align with the ICHOM minimum, if not how did they differ, and would they recommend modified or additional outcomes?. RESULTS: For some disciplines participants agreed with the ICHOM minimums but urged for earlier and more frequent intervention. Some clinicians felt that some of the ICHOM standards were compatible but that different ages were preferred and for others the ICHOM standards were acceptable but developmental stages should be preferred to absolute time points. CONCLUSION/IMPLICATIONS: Core outcomes for OFC were supported in principle but there are differences between the ICHOM recommendations and the 2002 WHO global consensus. The latter are established in many centres with historical archives of OFC outcome data, and it was concluded that with some modifications ICHOM could be moulded into useful core outcomes data for inter-centre comparisons worldwide.

Novel IRF6 variant in orofacial cleft patients from Durban, South Africa.

BACKGROUND: To date, there are over 320 variants identified in the IRF6 gene that cause Van der Woude syndrome or popliteal pterygium syndrome. We sequenced this gene in a South African orofacial cleft cohort to identify the causal IRF6 variants in our population. METHOD: Saliva samples from 100 patients with syndromic and non-syndromic CL ± P were collected. Patients were recruited from the cleft clinics at two public, tertiary hospitals in Durban, South Africa (SA), namely Inkosi Albert Luthuli Central Hospital (IALCH) and KwaZulu-Natal Children's Hospital (KZNCH). We prospectively sequenced the exons of IRF6 in 100 orofacial cleft cases, and where possible, we also sequenced the parents of the individuals to determine the segregation pattern. RESULTS: Two variants were identified; one novel (p.Cys114Tyr) and one known (p.Arg84His) missense variant in IRF6 gene were identified. The patient with the p.Cys114Tyr variant was non-syndromic with no clinical VWS phenotype expected of individuals with IRF6 coding variants, and the patient with the p.Arg84His had phenotypic features of popliteal pterygium syndrome. The p.Arg84His variant segregated in the family, with the father also being affected. CONCLUSIONS: This study provides evidence that IRF6 variants are found in the South African population. Genetic counselling is essential for affected families, particularly in the absence of a known clinical phenotype since it helps with the plans for future pregnancies.

Damaging Mutations in AFDN Contribute to Risk of Nonsyndromic Cleft Lip With or Without Cleft Palate.

Novel or rare damaging mutations have been implicated in the developmental pathogenesis of nonsyndromic cleft lip with or without cleft palate (nsCL ± P). Thus, we investigated the human genome for high-impact mutations that could explain the risk of nsCL ± P in our cohorts.We conducted next-generation sequencing (NGS) analysis of 130 nsCL ± P case-parent African trios to identify pathogenic variants that contribute to the risk of clefting. We replicated this analysis using whole-exome sequence data from a Brazilian nsCL ± P cohort. Computational analyses were then used to predict the mechanism by which these variants could result in increased risks for nsCL ± P.We discovered damaging mutations within the AFDN gene, a cell adhesion molecule (CAMs) that was previously shown to contribute to cleft palate in mice. These mutations include p.Met1164Ile, p.Thr453Asn, p.Pro1638Ala, p.Arg669Gln, p.Ala1717Val, and p.Arg1596His. We also discovered a novel splicing p.Leu1588Leu mutation in this protein. Computational analysis suggests that these amino acid changes affect the interactions with other cleft-associated genes including nectins (PVRL1, PVRL2, PVRL3, and PVRL4) CDH1, CTNNA1, and CTNND1.This is the first report on the contribution of AFDN to the risk for nsCL ± P in humans. AFDN encodes AFADIN, an important CAM that forms calcium-independent complexes with nectins 1 and 4 (encoded by the genes PVRL1 and PVRL4). This discovery shows the power of NGS analysis of multiethnic cleft samples in combination with a computational approach in the understanding of the pathogenesis of nsCL ± P.

Dental education at Dundee Dental Hospital and School - a notable past and inspiring future.

Dundee Dental Hospital and School has been present on Park Place, Dundee for over 100 years. During this time, it has been at the forefront of dental care and education, first as part of the University of St Andrews and subsequently the University of Dundee. This innovation continues with novel undergraduate curricula for dental and dental therapy students, providing early clinical experience and integrating clinical teaching with the appropriate sciences. We also offer several taught postgraduate programmes, popular particularly with international students. Dundee was at the forefront of the response to the COVID-19 pandemic, with the Scottish Dental Clinical Effectiveness Programme leading the world on guidance for safe clinical practice. Innovative solutions for the ongoing delivery of teaching and assessment also were developed. Research underpins teaching and the delivery of dental care and Dundee has an international reputation for its research portfolio. All of the above can only be achieved by close working relationships between the University and NHS, which will be strengthened further by the creation of the Dundee Dental Research Hospital and School. Our international reputation will continue to attract students and staff from across the world.

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.

Caries in children with and without orofacial clefting: A systematic review and meta-analysis.

This systematic review compared children's primary dentition caries experience for those with cleft lip and/or palate (CL/P) and without. Four databases were searched without date restriction for; cross-sectional studies comparing caries experience for children with CL/P to those without. Screening, data extraction and risk assessment were carried out independently (in duplicate). Meta-analyses used a random-effects model. Twenty studies (21 reports) fitting the inclusion criteria comprised 4647 children in primary dentition from 12 countries. For dmft (n = 3016 children; 15 groups), CL/P mean = 3.2; standard deviation = 2.22 and no CL/P mean dmft = 2.5; sd 1.53. For dmfs (n = 1095 children; 6 groups), CL/P mean = 4; sd = 3.5 and no CL/P mean = 3; sd = 2.8. For % caries experience (n = 1094 children; 7 groups), CL/P mean = 65%; sd = 20.8 and no CL/P mean = 52%; sd = 28.1. Meta-analysis showed higher caries experience in children with CL/P, standardised mean difference = 0.46; 95% CI = 0.15, 0.77. Studies' risk of bias was high (n = 7), medium (n-10) and low (n = 3). Children with CL/P had higher caries experience compared to those without CLP.

Novel GRHL3 Variants in a South African Cohort With Cleft Lip and Palate.

OBJECTIVE: The etiology of cleft palate (CP) is poorly understood compared with that of cleft lip with or without palate (CL ± P). Recently, variants in Grainyhead like transcription factor 3 (GRHL3) were reported to be associated with a risk for CP in European and some African populations including Nigeria, Ghana, and Ethiopia. In order to identify genetic variants that may further explain the etiology of CP, we sequenced GRHL3 in a South African population to determine if rare variants in GRHL3 are associated with the presence of syndromic or nonsyndromic CP. DESIGN: We sequenced the exons of GRHL3 in 100 cases and where possible, we sequenced the parents of the individuals to determine the segregation pattern and presence of de novo variants. SETTING: The cleft clinics from 2 public, tertiary hospitals in Durban, South Africa (SA), namely Inkosi Albert Luthuli Central Hospital and KwaZulu-Natal Children's Hospital. PATIENTS, PARTICIPANTS: One hundred patients with CL ± P and their parents. INTERVENTIONS: Saliva samples were collected. MAIN OUTCOME MEASURES: To ascertain the genetic variants in the GRHL3 gene in patients with CL ± P in SA. RESULTS: Five variants in GRHL3 were observed; 3 were novel and 2 were known variants. The novel variants were intronic variants (c.1062 + 77A>G and c.627 + 1G>A) and missense variant (p.Asp169Gly). CONCLUSIONS: This study provides further evidence that variants in GRHL3 contribute to the risk of nonsyndromic CP in African populations, specifically, in the South African population.

Variant analyses of candidate genes in orofacial clefts in multi-ethnic populations.

OBJECTIVES: Cleft lip with/without cleft palate and cleft palate only is congenital birth defects where the upper lip and/or palate fail to fuse properly during embryonic facial development. Affecting ~1.2/1000 live births worldwide, these orofacial clefts impose significant social and financial burdens on affected individuals and their families. Orofacial clefts have a complex etiology resulting from genetic variants combined with environmental covariates. Recent genome-wide association studies and whole-exome sequencing for orofacial clefts identified significant genetic associations and variants in several genes. Of these, we investigated the role of common/rare variants in SHH, RORA, MRPL53, ACVR1, and GDF11. MATERIALS AND METHODS: We sequenced these five genes in 1255 multi-ethnic cleft lip with/without palate and cleft palate only samples in order to find variants that may provide potential explanations for the missing heritability of orofacial clefts. Rare and novel variants were further analyzed using in silico predictive tools. RESULTS: Ninteen total variants of interest were found, with variant types including stop-gain, missense, synonymous, intronic, and splice-site variants. Of these, 3 novel missense variants were found, one in SHH, one in RORA, and one in GDF11. CONCLUSION: This study provides evidence that variants in SHH, RORA, MRPL53, ACVR1, and GDF11 may contribute to risk of orofacial clefts in various populations.

Development of intra-oral automated landmark recognition (ALR) for dental and occlusal outcome measurements.

BACKGROUND: Previous studies embracing digital technology and automated methods of scoring dental arch relationships have shown that such technology is valid and accurate. To date, however there is no published literature on artificial intelligence and machine learning to completely automate the process of dental landmark recognition. OBJECTIVES: This study aimed to develop and evaluate a fully automated system and software tool for the identification of landmarks on human teeth using geometric computing, image segmenting, and machine learning technology. METHODS: Two hundred and thirty-nine digital models were used in the automated landmark recognition (ALR) validation phase, 161 of which were digital models from cleft palate subjects aged 5 years. These were manually annotated to facilitate qualitative validation. Additionally, landmarks were placed on 20 adult digital models manually by 3 independent observers. The same models were subjected to scoring using the ALR software and the differences (in mm) were calculated. All the teeth from the 239 models were evaluated for correct recognition by the ALR with a breakdown to find which stages of the process caused the errors. RESULTS: The results revealed that 1526 out of 1915 teeth (79.7%) were correctly identified, and the accuracy validation gave 95% confidence intervals for the geometric mean error of [0.285, 0.317] for the humans and [0.269, 0.325] for ALR-a negligible difference. CONCLUSIONS/IMPLICATIONS: It is anticipated that ALR software tool will have applications throughout clinical dentistry and anthropology, and in research will constitute an accurate and objective tool for handling large datasets without the need for time intensive employment of experts to place landmarks manually.

Genome-Wide Scan for Parent-of-Origin Effects in a sub-Saharan African Cohort With Nonsyndromic Cleft Lip and/or Cleft Palate (CL/P).

OBJECTIVE: Nonsyndromic cleft lip and/or cleft palate (NSCL/P) have multifactorial etiology where genetic factors, gene-environment interactions, stochastic factors, gene-gene interactions, and parent-of-origin effects (POEs) play cardinal roles. POEs arise when the parental origin of alleles differentially impacts the phenotype of the offspring. The aim of this study was to identify POEs that can increase risk for NSCL/P in humans using a genome-wide dataset. METHODS: The samples (174 case-parent trios from Ghana, Ethiopia, and Nigeria) included in this study were from the African only genome wide association studies (GWAS) that was published in 2019. Genotyping of individual DNA using over 2 million multiethnic and African ancestry-specific single-nucleotide polymorphisms from the Illumina Multi-Ethnic Genotyping Array v2 15070954 A2 (genome build GRCh37/hg19) was done at the Center for Inherited Diseases Research. After quality control checks, PLINK was employed to carry out POE analysis employing the pooled subphenotypes of NSCL/P. RESULTS: We observed possible hints of POEs at a cluster of genes at a 1 mega base pair window at the major histocompatibility complex class 1 locus on chromosome 6, as well as at other loci encompassing candidate genes such as ASB18, ANKEF1, AGAP1, GABRD, HHAT, CCT7, DNMT3A, EPHA7, FOXO3, lncRNAs, microRNA, antisense RNAs, ZNRD1, ZFAT, and ZBTB16. CONCLUSION: Findings from our study suggest that some loci may increase the risk for NSCL/P through POEs. Additional studies are required to confirm these suggestive loci in NSCL/P etiology.