Novel <i>IRF6 </i>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

Novel <i>GREM1 </i>Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate

Objective: Cleft lip and/or cleft palate (CL/P) are congenital anomalies of the face and have multifactorial etiology, with both environmental and genetic risk factors playing crucial roles. Though at least 40 loci have attained genomewide significant association with nonsyndromic CL/P, these loci largely reside in noncoding regions of the human genome, and subsequent resequencing studies of neighboring candidate genes have revealed only a limited number of etiologic coding variants. The present study was conducted to identify etiologic coding variants in GREM1, a locus that has been shown to be largely associated with cleft of both lip and soft palate. Patients and Method: We resequenced DNA from 397 sub-Saharan Africans with CL/P and 192 controls using Sanger sequencing. Following analyses of the sequence data, we observed 2 novel coding variants in GREM1. These variants were not found in the 192 African controls and have never been previously reported in any public genetic variant database that includes more than 5000 combined African and African American controls or from the CL/P literature. Results: The novel variants include p.Pro164Ser in an individual with soft palate cleft only and p.Gly61Asp in an individual with bilateral cleft lip and palate. The proband with the p.Gly61Asp GREM1 variant is a van der Woude (VWS) case who also has an etiologic variant in IRF6 gene. Conclusion: Our study demonstrated that there is low number of etiologic coding variants in GREM1, confirming earlier suggestions that variants in regulatory elements may largely account for the association between this locus and CL/P. </jats:sec

Use of information and communication technology among dental students and registrars at the faculty of dental sciences, university of Lagos

The aim of this study was to investigate the use of information technology amongst dental students, dental nursing students and resident doctors in training at the faculty of dental Surgery University of Lagos. A structured questionnaire was distributed to 58 clinical dental students in 4th and 5th years of training in the 2010/2011 academic year, 36 dental nursing students and 63 resident doctors undergoing specialist training. All participants have access to the computers, 2.5% within the University and 31% at home and internet cafes and about 50% have the basic skills required. A significant difference was observed between the resident doctors and clinical dental students (P = 0.003), between resident doctors and dental nursing students (P = 0.0001) when the use of computer for study was compared. Over 95% of participants have access to internet and about 50% of them use the internet for their studies. A significant difference (P = 0.005) was observed between clinical dental students and dental nursing students that use the internet and word processing. The resident doctors used the computers for multimedia and MedLine search tools more than clinical dental students (P = 0.004) and dental nursing students (0.0006). The findings of the study show that dental students and resident doctors in training have the requisite knowledge to operate the computer for use in their study and personal activities

Identification of Paternal Uniparental Disomy on Chromosome 22 and a De-novo Deletion on Chromosome 18 in Individuals with Orofacial Clefts

Background: Orofacial clefts are the most common malformations of the head and neck region. Genetic and environmental factors have been implicated in the etiology of these traits.Methods: We recently conducted genotyping of individuals from the African population using the multiethnic genotyping array (MEGA) to identify common genetic variation associated with nonsyndromic orofacial clefts. The data cleaning of this dataset allowed for screening of annotated sex versus genetic sex, confirmation of identify by descent and identification of large chromosomal anomalies.Results: We identified the first reported orofacial cleft case associated with paternal uniparental disomy (patUPD) on chromosome 22. We also identified a de novo deletion on chromosome 18. In addition to chromosomal anomalies, we identified cases with molecular karyotypes suggesting Klinefelter syndrome, Turner syndrome and Triple X syndrome.Conclusion: Observations from our study support the need for genetic testing when clinically indicated in order to exclude chromosomal anomalies associated with clefting. The identification of these chromosomal anomalies and sex aneuploidies is important in genetic counseling for families that are at risk. Clinicians should share any identified genetic findings and place them in context for the families during routine clinical visits and evaluations.</p

Association studies and direct DNA sequencing implicate some known genetic susceptibility loci in the etiology of nonsyndromic orofacial clefts in sub-Saharan African populations

Orofacial clefts (OFCs) are congenital dysmorphologies of the human face and oral cavity, with a global incidence of 1 per 700 live births. These anomalies exhibit multifactorial pattern of inheritance, with both genetic and environmental factors playing crucial roles. Many loci have been implicated in the aetiology of nonsyndromic cleft lip with or without cleft palate (NSCL/P) in populations of Asian and European ancestries through genome-wide association studies (GWAS) and candidate gene studies. However, few populations of African descent have been studied to date. Here, we show evidence of association of some loci with NSCL/P and nonsyndromic cleft palate only (NSCPO) in cohorts from Africa (Ghana, Ethiopia and Nigeria). We genotyped 48 SNPs that were selected from previous GWAS and candidate gene studies. These markers were successfully genotyped on 701 NSCL/P and 163 NSCPO cases, 1070 unaffected relatives and 1078 unrelated controls. We also directly sequenced 7 genes in 184 nonsyndromic OFC (NSOFC) cases and 96 controls from Ghana. Population-specific associations were observed in the case-control analyses of the sub-populations, with West African subpopulations (Ghana and Nigeria) showing similar pattern of associations. In meta-analyses of the case-control cohort, PAX7 (rs742071, p=5.10×10-03), 8q24 (rs987525, p=1.22×10-03) and VAX1 (rs7078160, p=0.04) were nominally associated with NSCL/P; MSX1 (rs115200552, p=0.01), TULP4 (rs651333, p=0.04), CRISPLD2 (rs4783099, p=0.02) and NOG1 (rs17760296, p=0.04) were nominally associated with NSCPO. Moreover, 7 loci exhibited evidence of threshold over-transmission in NSOFC cases in both transmission disequilibrium test (TDT) and family-based association for disease traits (DFAM) analyses. Through DNA sequencing, we also identified two novel, rare, potentially pathogenic variants (p.Asn323Asp and p.Lys426IlefsTer6) in ARHGAP29. In conclusion, we have shown evidence of association of many loci with NSCL/P and NSCPO. To the best of our knowledge, our study is the first to demonstrate any of these association signals in any African population.<br/

Descriptive epidemiology of salivary gland neoplasms in Nigeria: An AOPRC multicenter tertiary hospital study

Objectives Accurate diagnosis of salivary gland neoplasms (SGN) in many centers in Africa is limited by poor diagnostic resources and ancillary services. Hence, we have carried out a multicenter epidemiological study to understand the true burden of SGN in Nigeria. Method In this descriptive cross-sectional study, we have deployed resources available to members of the African Oral Pathology Consortium (AOPRC) to examine the burden of salivary gland lesions in Nigeria, using a multicenter approach. Data from seven major tertiary health institutions in northern, western, and southern Nigeria were generated using a standardized data extraction format and analyzed using the Epi-info software (Version 7.0, Atlanta, USA). Result Of the 497 cases examined across the seven centers, we observed that SGN occurred more in females than males. Overall, pleomorphic salivary adenoma (PA) was found to be the most common. PA was found to be the commonest benign SGN while adenocystic carcinoma (ADCC) was the commonest malignant SGN. Regional variations were observed for age group, diagnosis, and gender distribution. Significant statistical differences were found between males and females for malignant SGNs (p-value=0.037). Conclusion We found regional variation in the pattern of distribution of SGN in Nigeria. This is the largest multicenter study of SGN in Nigeria, and our findings are robust and representative of the epidemiology of this neoplasm in Nigeria

MTHFR promoter methylation might mitigate the effect of smoking at the level of LINE-1 in cleft lip tissues:A preliminary study

Background: The medial and maxillary aspects of the upper lip originate at separate embryonic stages and therefore may experience different maternal exposure patterns which may affect methylation. Based on this hypothesis, we investigated the level of methylation of the methylene tetrahydrofolate reductase promoter gene (mMTHFR) in tissues from cleft lip, and mMTHFR levels by MTHFR c.677C &gt; T genotype. We further investigated whether mMTHFR mitigates the effect of smoking on long interspersed nuclear element (LINE-1) methylation in these tissues.Methods: DNA extracted from medial and lateral tissues of 26 infants with nonsyndromic cleft lip with or without cleft palate (nsCL/P) was bisulfite converted and mMTHFR was measured on a pyrosequenser. LINE-1 methylation and MTHFR c.677C &gt; T genotype data were obtained in our previous study.Results: There was no substantial difference in mMTHFR (p =.733) and LINE-1 (p =.148) between the two tissues. mMTHFR was not influenced by MTHFR c.677C &gt; T genotype, but there was suggestive evidence that the difference was larger among infants exposed to maternal smoking compared to nonexposed. LINE-1 methylation differences were significant (p =.025) in infants born to nonsmoking mothers, but this was not apparent (p =.872) in infants born to mothers who smoked. Our Pearson's correlation analysis suggested a weak inverse association between mMTHFR and LINE-1 (r = −.179, p =.381).Conclusion: Our preliminary observation of differences in patterns of mMTHFR levels in lip tissue suggests the interplay of gene and environment in the establishment of methylation in tissues at both sides of cleft lip. This requires investigation in a larger cohort, integrated with metabolic assessment.</p

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&gt;G and c.627 + 1G&gt;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.</p

Pulse rate during running 5 laps: comparative study before and after dehydration?

Background and Study Aim. Dehydration is a condition where there is a lack of fluid in the body, accompanied by disturbances in the body's metabolic processes. This study aims to prove the effect of dehydration on 5 lap running by comparing the pulse rate before and after dehydration. Materials and Methods. This study used an experimental method. The population in this research is Tanjungpura University sports students. Purposive sampling technique so that a sample of 19 students was obtained. The sample consists of 4 women and 15 men. In the research, the implementation procedure will be to measure 2000 meter running performance before and after losing fluid, weighing body weight to precision ounces. Analysis was assisted using SPSS 26. Results. The results of the analysis showed a significance value of 0.000 <0.05, which is a significant difference between the pulse rate before and after dehydration when running 5 laps. The pulse rate after dehydration tended to be higher, indicating an increased cardiac workload during physical activity. Conclusions. This study concludes that dehydration has a direct influence on pulse rate when running 5 laps. The existence of this difference highlights the importance of maintaining an optimal hydration state in supporting a healthy cardiovascular response during physical activity, particularly in high-intensity exercise such as running. These findings can be used as a basis for the development of more effective hydration strategies in the context of aerobic physical activity