Publications by authors named "Azeez Butali"

51 Publications

Correlation Between Height and Impacted Third Molars and Genetics Role in Third Molar Impaction.

J Maxillofac Oral Surg 2021 Mar 31;20(1):149-153. Epub 2020 Jan 31.

Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, USA.

Aim: This study sought to evaluate the relationship between height of an individual and the presence of impaction of maxillary and mandibular third molars, and to determine the role of genetics in third molar impaction.

Materials And Methods: This was a case-control study, with cases consisted of 200 subjects with third molar impactions; and 200 controls without third molar impactions. Height of subjects was measured, and saliva samples were collected from all the subjects. DNA was extracted from saliva samples. To investigate the role of selected genes in the etiology of third molar impactions, Taqman Genotyping using SNPs identified for jaw growth, height and tooth agenesis was employed. Five candidate genes were investigated using 11 markers (SNPs).

Results: The mean height of cases was significantly lower than that of the control subjects (= 0.04). No difference was found in allele frequency between cases and controls for 10 of the 11 SNPs. However, for rs6504591 the value was near significance (= 0.07) with odd ratio of 2.131. Subjects with lower third molar impactions were significantly shorter than those who have fully erupted third molars.

Conclusions: Subjects with lower third molar impactions were significantly shorter than those who have fully erupted third molars. We observed that individuals with third molar impaction tend to have T allele at the locus, suggesting that the T allele at the locus may increase the risk for having an impacted third molar. The rs6504591 G/T variation on human chromosome 17 (WNT9B gene) appears to increase risk by twofolds for impaction albeit with inability to detect significance due to small sample size.
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http://dx.doi.org/10.1007/s12663-020-01336-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7855106PMC
March 2021

A national window on critical thinking by dental educators following an ADEA webinar.

J Dent Educ 2021 Jan 21. Epub 2021 Jan 21.

Department of Oral Pathology, Radiology, and Medicine, University of Iowa College of Dentistry and Dental Clinics, Iowa City, Iowa, USA.

Purpose: Critical thinking is an essential skill for the dentist, yet little has surfaced to define the outcome, guide learning, and assess performance. On June 16, 2020, the American Dental Education Association (ADEA) sponsored a 1-hour webinar on Critical thinking with 600 attendees. To report input from a national cohort of dental educators responding to a model for critical thinking guidance.

Methods: Critical thinking concepts with explicit skillsets were presented. Attendees gave Likert responses on importance and confidence defining outcome. At the end of the webinar, attendees were asked in an open-ended format what their "take away" was.

Results: One hundred and five responded to a Likert scale question on how important critical thinking is, with 93% giving a 5. To the question on how well have you figured out how to define the outcome, guide learning, and assess performance, 53% gave a 3 and 21% gave a 2 (χ = 151; P < 0.01) From 121 "take away" responses, 79 reiterated the session's central theme with comments on emulating the thought process of the expert or articulating a skillset. In a separate classification of the same "take away," responses oriented to common domains of education nomenclature. No alternative critical thinking model for articulating the outcome, guiding learning, and assessing performance was evident in any of the 121 take away responses.

Conclusions: Results are interpreted as an opportunity moment for dental education to collectively develop additional critical thinking models.
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http://dx.doi.org/10.1002/jdd.12530DOI Listing
January 2021

Prevalence of Torus Palatinus and association with dental arch shape in a multi-ethnic cohort.

Homo 2020 Nov;71(4):273-280

Center for Craniofacial and Dental Genetics, Department of Oral Biology, University of Pittsburgh, Pittsburgh, PA, USA.

Torus Palatinus (TP) is a bony projection located on the oral surface of the hard palate. The trait is typically benign, has an unknown etiology, and varies widely in phenotypic expression. Prior studies suggest differences in TP prevalence by sex and ancestry, but the reported rates vary, even within a single ancestral group. We assessed the prevalence of TP and its association with palatal shape in a large multi-ethnic cohort of normal individuals. 1102 adults were included (625 with European ancestry, 377 with West African anscestry, and 100 with East Asian ancestry). 3D digital dental casts were obtained and rated. TP frequencies were compared between sexes and/or ethnicities using Chi-squared tests. Dental cast models were then landmarked, and canonical variates analysis was performed to test for shape differences between those with and without TP. Females had a significantly higher rate of TP than males across all three ancestral groups (p≤0.004). In males, no significant differences were found among ethnicities. Ancestral differences in TP frequency were driven by females, with East Asians having the highest rate (34.69%), followed by Europeans (24.88%) and West Africans (15.22%). Shape differences were found only in Asians and Africans, indicated a shorter and wider palate in presence of TP. Ethnic differences in TP frequency were present only in females. Further, females have considerably higher rates of TP than males in each population tested. Further studies of TP at earlier time-points and in connection to other aspects of craniofacial growth may shed light on these sex and ethnic differences.
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http://dx.doi.org/10.1127/homo/2020/1316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7674192PMC
November 2020

Parents of Children With Nonsyndromic Orofacial Clefting Show Altered Palate Shape.

Cleft Palate Craniofac J 2020 Oct 28:1055665620967235. Epub 2020 Oct 28.

Center for Craniofacial and Dental Genetics, Department of Oral Biology, 212605University of Pittsburgh, Pittsburgh, PA, USA.

Objective: The unaffected relatives of individuals with nonsyndromic orofacial clefts have been shown to exhibit subtle craniofacial differences compared with the general population. Here, we investigate whether these morphological differences extend to the shape of the palate.

Design: We conducted a geometric morphometric analysis to compare palate shape in the clinically unaffected parents of children with nonsyndromic cleft lip with or without cleft palate and adult controls of European, Asian, and African ancestry. We conducted pairwise group comparisons using canonical variates analysis, and then confirmed and characterized findings of shape differences using Euclidean distance matrix analysis.

Results: Significant differences in palate shape were detected in unaffected mothers (but not fathers) compared to demographically matched controls. The differences in shape were ancestry-specific; mothers of Asian-derived and African-derived ancestry showed wider and shorter palates with higher posterior palatal vaults, while mothers of European-derived ancestry showed narrower palates with higher anterior palatal vaults.

Conclusions: Our findings suggest that altered palate shape is a subclinical phenotypic feature, which may be indicative of elevated orofacial cleft risk. The risk phenotype varied by sex and ancestry, suggesting possible etiologic heterogeneity among demographic groups. Understanding the genetic basis of these informative palate shape traits may reveal new genes and pathways relevant to nonsyndromic orofacial clefting.
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http://dx.doi.org/10.1177/1055665620967235DOI Listing
October 2020

Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome.

Mol Genet Genomic Med 2020 08 17;8(8):e1355. Epub 2020 Jun 17.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.

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.
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http://dx.doi.org/10.1002/mgg3.1355DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434609PMC
August 2020

Two critical thinking models-probing questions and conceptualization-adding 4 skillsets to the teacher's armamentarium.

J Dent Educ 2020 Jul 18;84(7):733-741. Epub 2020 May 18.

Department of Prosthodontics, University of Iowa College of Dentistry and Dental Clinics, Iowa City, IA, USA.

Critical thinking is ubiquitous in patient care. One track for critical thinking develops skillsets emulating the thought process of the master clinician using probing questions and has been offered in treatment planning, literature search, and critique, risk assessment in caries and geriatrics, technology decision-making, EBD, and IPP. This paper offers 2 additional critical thinking skillsets following this emulation model in social work and ethics. Conceptualization, another form of critical thinking, is also ubiquitous in health care, yet almost no literature exists to guide learning and assess performance on conceptualization. This paper introduces for discussion 2 examples of conceptualization-"How and how much does this situation differ from the ideal?" and "How does the student/practitioner conceptualize the outcome prior to the imminent procedure?" -used continually by the practitioner in patient care situations. The result is 4 additional critical thinking skillsets at different stages of development in the armamentarium for the teacher.
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http://dx.doi.org/10.1002/jdd.12177DOI Listing
July 2020

Breastfeeding Practices Among Mothers of Children With Orofacial Clefts in an African Cohort.

Cleft Palate Craniofac J 2020 Aug 15;57(8):1018-1023. Epub 2020 Apr 15.

Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Idi-Araba, Nigeria.

Objective: To carry out a survey of breastfeeding practices and related challenges among mothers with orofacial cleft babies attending the cleft clinic of a tertiary health institution.

Methodology: This was a cross-sectional descriptive study using an interviewer-administered questionnaire. Sample population was all mothers of babies aged between 1 and 18 months with nonsyndromic orofacial clefts attending the cleft clinic of a tertiary health institution in Nigeria.

Result: A total of 65 mothers participated in the study. Initiation of breastfeeding was reported by the majority (83%, n = 54) of the mothers, and only 18.5% (n = 10) of this proportion continued exclusive breastfeeding. Inability of the babies to suck was reported by 46% (n = 30) of the mothers as being the most important challenge in breastfeeding. There was a significant correlation between the type of cleft and challenge in breastfeeding (Fisher exact = .001). Sixty-three percent (n = 41) of the mothers reported they received no counseling on overcoming challenges associated with feeding their babies with a cleft at the facility where they delivered. Sixty-nine percent (n = 45) reported they first received nutritional information from the cleft clinic at presentation. The most adopted substitute for breastfeeding was the use of regular feeding bottles (n = 24, 43.6%).

Conclusion: Rate of initiation of breastfeeding for children with orofacial clefts in this African cohort is higher than reported in other populations despite the low level of nutritional counseling of the mothers after delivery.
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http://dx.doi.org/10.1177/1055665620919312DOI Listing
August 2020

A Preexperimental Study to Assess the Impact of an Interdisciplinary Educational Intervention on Nurses' Knowledge of Perinatal and Infant Oral Health Care.

J Int Soc Prev Community Dent 2019 Nov-Dec;9(6):619-629. Epub 2019 Nov 4.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry and Dental Clinics, University of Iowa, Iowa, USA.

Objective: The objective of this study was to assess the impact of an interdisciplinary educational intervention on the knowledge of nursing practitioners regarding perinatal and infant oral health (PIOH) care.

Materials And Methods: This was a preexperimental study conducted among nursing practitioners in Lagos, Nigeria. Participants received hands-on training and didactic lectures, which included dental caries etiology and risk factors; oral hygiene and dietary education; teething and its management; dental trauma and its prevention; nonnutritive habits; screening, referrals, and counseling; and fluoride varnish application. Knowledge of the trainees was assessed using pre- and posttest questionnaires. Level of statistical significance was set at < 0.05.

Results: Overall, 110 nurses participated in the study with a mean age of 40.9 ± 10.8 years; 106 (96.4%) were females. Approximately 88% of the participants had not received formal training on PIOH. The baseline mean scores of the participants' knowledge on oral hygiene, teething, trauma, caries, and oral habits were 4.31 ± 1.9, 9.84 ± 2.6, 2.59 ± 1.7, 4.24 ± 1.8, and 1.45 ± 0.6, respectively; this increased significantly ( < 0.001) following the educational intervention with posttest mean scores as 7.58 ± 0.8, 11.79 ± 1.3, 4.34 ± 1.9, 6.19 ± 1.8, and 1.82 ± 0.4 and six-month evaluation scores as 6.21 ± 1.8,7 10.27 ± 3.1, 4.39 ± 1.5, 5.91 ± 1.8, and 1.79 ± 0.5, respectively. Overall posttest (31.4 ± 4.2) and six-month (28.6 ± 6.2) knowledge scores were significantly higher than the pretest values (22.4 ± 4.8, < 0.001). At the six-month post-intervention survey, 84% of the nurses reported inclusion of PIOH education in their routine general health education sessions.

Conclusion: There was a positive impact of the educational intervention as evidenced by an increase in the knowledge of the nurses on PIOH care and the inclusion of PIOH education in their general health education. A slight decline between posttest and six-month evaluation scores indicates a need for continuous education and evaluation.
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http://dx.doi.org/10.4103/jispcd.JISPCD_144_19DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6905320PMC
November 2019

SPECC1L regulates palate development downstream of IRF6.

Hum Mol Genet 2020 03;29(5):845-858

Department of Anatomy and Cell Biology, University of Kansas Medical Center, Kansas City, KS 66160, USA.

SPECC1L mutations have been identified in patients with rare atypical orofacial clefts and with syndromic cleft lip and/or palate (CL/P). These mutations cluster in the second coiled-coil and calponin homology domains of SPECC1L and severely affect the ability of SPECC1L to associate with microtubules. We previously showed that gene-trap knockout of Specc1l in mouse results in early embryonic lethality. We now present a truncation mutant mouse allele, Specc1lΔC510, that results in perinatal lethality. Specc1lΔC510/ΔC510 homozygotes showed abnormal palate rugae but did not show cleft palate. However, when crossed with a gene-trap allele, Specc1lcGT/ΔC510 compound heterozygotes showed a palate elevation delay with incompletely penetrant cleft palate. Specc1lcGT/ΔC510 embryos exhibit transient oral epithelial adhesions at E13.5, which may delay shelf elevation. Consistent with oral adhesions, we show periderm layer abnormalities, including ectopic apical expression of adherens junction markers, similar to Irf6 hypomorphic mutants and Arhgap29 heterozygotes. Indeed, SPECC1L expression is drastically reduced in Irf6 mutant palatal shelves. Finally, we wanted to determine if SPECC1L deficiency also contributed to non-syndromic (ns) CL/P. We sequenced 62 Caucasian, 89 Filipino, 90 Ethiopian, 90 Nigerian and 95 Japanese patients with nsCL/P and identified three rare coding variants (p.Ala86Thr, p.Met91Iso and p.Arg546Gln) in six individuals. These variants reside outside of SPECC1L coiled-coil domains and result in milder functional defects than variants associated with syndromic clefting. Together, our data indicate that palate elevation is sensitive to deficiency of SPECC1L dosage and function and that SPECC1L cytoskeletal protein functions downstream of IRF6 in palatogenesis.
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http://dx.doi.org/10.1093/hmg/ddaa002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7104672PMC
March 2020

Whole genome sequencing of orofacial cleft trios from the Gabriella Miller Kids First Pediatric Research Consortium identifies a new locus on chromosome 21.

Hum Genet 2020 Feb 17;139(2):215-226. Epub 2019 Dec 17.

Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Bridgeside Point Suite 500, 100 Technology Dr., Pittsburgh, PA, 15219, USA.

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 the genetic etiology of non-syndromic OFCs is only partially determined. Here, we analyze whole genome sequence (WGS) data for association with risk of OFCs in European and Colombian families selected from a multicenter family-based OFC study. This is the first large-scale WGS study of OFC in parent-offspring trios, and a part of the Gabriella Miller Kids First Pediatric Research Program created for the study of childhood cancers and structural birth defects. WGS provides deeper and more specific genetic data than using imputation on present-day single nucleotide polymorphic (SNP) marker panels. Genotypes of case-parent trios at single nucleotide variants (SNV) and short insertions and deletions (indels) spanning the entire genome were called from their sequences using human GRCh38 genome assembly, and analyzed for association using the transmission disequilibrium test. Among genome-wide significant associations, we identified a new locus on chromosome 21 in Colombian families, not previously observed in other larger OFC samples of Latin American ancestry. This locus is situated within a region known to be expressed during craniofacial development. Based on deeper investigation of this locus, we concluded that it contributed risk for OFCs exclusively in the Colombians. This study reinforces the ancestry differences seen in the genetic etiology of OFCs, and underscores the need for larger samples when studying for OFCs and other birth defects in populations with diverse ancestry.
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http://dx.doi.org/10.1007/s00439-019-02099-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6981325PMC
February 2020

The Role of Environmental Factors in the Etiology of Nonsyndromic Orofacial Clefts.

J Craniofac Surg 2020 Jan/Feb;31(1):113-116

Department of Preventive Medicine, School of Public Health, College of Health Sciences, Addis Ababa University, Addis Ababa, Ethiopia.

Background: Nonsyndromic orofacial clefts (NSOFCs) represent the most common congenital anomalies in the head and neck region. Multiple factors contribute to the occurrence of this anomaly. The etiology of NSOFCs in the Ethiopian population has not been investigated prior to this study.

Aims Of The Study: To assess the role of maternal environmental factors in the occurrence of NSOFCs in the Ethiopian Population.

Methods: The authors used unmatched case control study design and evaluated the role of environmental factors to the occurrence of NSOFCs in the Ethiopian population. The participants were recruited from the same institution (Yekatit 12 Hospital Medical College). The authors studied 760 mothers (359 mothers of children born with NSOFCs and 401 mothers of children born without any congenital anomalies). Univariate and multivariate logistic regression analyses were used to calculate relative risk by odds ratio and 95% confidence interval.

Results: Mothers who gave history of bronchial asthma and mothers who were admitted for threatened abortion had a higher risk of delivering a child with NSOFCS P value=0.013; AOR=0.194, 95% CI [0.053-0.712], P value <0.001; AOR= 0.179, 95% CI [0.091-0.352] respectively. Higher number of children with NSOFCs were born to mothers who were exposed to diagnostic X-ray investigation during early pregnancy than those who were not exposed P value 0.048; AOR=0.375, 95% CI [0.142-0.990].

Conclusion: Maternal exposure to diagnostic x-ray, maternal chronic illness like bronchial asthma and threatened abortion were found to be associated with the occurrence of NSOFCS in the studied population.
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http://dx.doi.org/10.1097/SCS.0000000000005924DOI Listing
March 2020

Six2 regulates Pax9 expression, palatogenesis and craniofacial bone formation.

Dev Biol 2020 02 23;458(2):246-256. Epub 2019 Nov 23.

Department of Anatomy and Cell Biology and the Craniofacial Anomalies Research Center, The University of Iowa, Iowa City, IA, 52242, USA; Iowa Institute of Oral Health Research, University of Iowa, Iowa City, IA, 52242, USA. Electronic address:

In this study, we investigated the role of the transcription factor Six2 in palate development. Six2 was selected using the SysFACE tool to predict genes from the 2p21 locus, a region associated with clefting in humans by GWAS, that are likely to be involved in palatogenesis. We functionally validated the predicted role of Six2 in palatogenesis by showing that 22% of Six2 null embryos develop cleft palate. Six2 contributes to palatogenesis by promoting mesenchymal cell proliferation and regulating bone formation. The clefting phenotype in Six2 embryos is similar to Pax9 null embryos, so we examined the functional relationship of these two genes. Mechanistically, SIX2 binds to a PAX9 5' upstream regulatory element and activates PAX9 expression. In addition, we identified a human SIX2 coding variant (p.Gly264Glu) in a proband with cleft palate. We show this missense mutation affects the stability of the SIX2 protein and leads to decreased PAX9 expression. The low penetrance of clefting in the Six2 null mouse combined with the mutation in one patient with cleft palate underscores the potential combinatorial interactions of other genes in clefting. Our study demonstrates that Six2 interacts with the developmental gene regulatory network in the developing palate.
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http://dx.doi.org/10.1016/j.ydbio.2019.11.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7568837PMC
February 2020

Comparison of students' perception of problem-based learning and traditional teaching method in a Nigerian dental school.

Eur J Dent Educ 2020 May 6;24(2):207-212. Epub 2019 Dec 6.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry University of Iowa, Iowa City, IA, USA.

Objectives: To evaluate the perceptions of dental students on problem-based learning, PBL, in comparison with the traditional lecture (TL) method.

Methods: This comparative study was conducted amongst 72 dental undergraduates. PBL was introduced to the students before the commencement of course. PBL method was used by the student to learn about cariology, whilst other lecture topics were taught by the TL. Students were not informed at the beginning of the course about end of course assessment of learning and teaching methods to limit their bias. The study was approved by the institution's ethics committee, and informed consent was obtained from participants at the end of the course to recruit them into the study. The students worked in small groups to solve tasks on clinical case scenarios. Four class sessions were held for presentations and discussions. The students' perceptions concerning the two teaching methods were sought by the use of an anonymously completed questionnaire. Six perceived factors that influenced the teaching and learning process were extracted from the twenty-two-perception-item questionnaire using factor analysis. Paired sample t test was used for comparison of means.

Results: The highest mean scores for all six perceived factors were observed in the PBL method. There were statistically significant differences (P < .05) between PBL and TL teaching methods for all the perceived factors; ("Challenge critical thinking," "Communication with peers," "Usefulness as pedagogical method," "Organization" and "Interaction between students and tutors") except for the perceived factor "Adequacy of teaching." The mean for most of the perception items was highest in the PBL method compared to TL. The perception item "Able to provide intellectual stimulation" had the highest mean score (4.21 ± 0.76) for the PBL method, whilst it was "Laboratory exercise" (4.14 ± 0.68) for TL.

Conclusions: Students' perception of the two educational methods investigated showed a preference for the PBL method. The students felt that PBL provided a higher ability for intellectual stimulation.
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http://dx.doi.org/10.1111/eje.12486DOI Listing
May 2020

Affect Dental Morphogenesis Resulting in X-linked Taurodontism, Microdontia and Dens-Invaginatus.

Front Genet 2019 20;10:800. Epub 2019 Sep 20.

Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, United States.

The etiology of dental anomalies is multifactorial; and genetic and environmental factors that affect the dental lamina have been implicated. We investigated two families of European ancestry in which males were affected by taurodontism, microdontia and dens invaginatus. In both families, males were related to each other unaffected females. A linkage analysis was conducted in a New Zealand family, followed by exome sequencing and focused analysis of the X-chromosome. In a US family, exome sequencing of the X-chromosome was followed by Sanger sequencing to conduct segregation analyses. We identified two independent missense variants in that segregate in affected males and female carriers. The variant in a New Zealand family (p.Asp371His) predicts the substitution of a residue in the motor domain of the protein while the one in a US family (p.Arg771Lys) predicts the substitution of a residue in the domain that interacts with Protein Regulator of Cytokinesis 1 (PRC1). We demonstrated that the gene is expressed in the developing tooth bud during development, and that the p.Arg771Lys variant influences cell migration in an assay. These data implicate missense variations in in a pathogenic mechanism that causes taurodontism, microdontia and dens invaginatus phenotypes.
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http://dx.doi.org/10.3389/fgene.2019.00800DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764483PMC
September 2019

A systematic genetic analysis and visualization of phenotypic heterogeneity among orofacial cleft GWAS signals.

Genet Epidemiol 2019 09 6;43(6):704-716. Epub 2019 Jun 6.

Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, Georgia.

Phenotypic heterogeneity is a hallmark of complex traits, and genetic studies of such traits may focus on them as a single diagnostic entity or by analyzing specific components. For example, in orofacial clefting (OFC), three subtypes-cleft lip (CL), cleft lip and palate (CLP), and cleft palate (CP) have been studied separately and in combination. To further dissect the genetic architecture of OFCs and how a given associated locus may be contributing to distinct subtypes of a trait we developed a framework for quantifying and interpreting evidence of subtype-specific or shared genetic effects in complex traits. We applied this technique to create a "cleft map" of the association of 30 genetic loci with three OFC subtypes. In addition to new associations, we found loci with subtype-specific effects (e.g., GRHL3 [CP], WNT5A [CLP]), as well as loci associated with two or all three subtypes. We cross-referenced these results with mouse craniofacial gene expression datasets, which identified additional promising candidate genes. However, we found no strong correlation between OFC subtypes and expression patterns. In aggregate, the cleft map revealed that neither subtype-specific nor shared genetic effects operate in isolation in OFC architecture. Our approach can be easily applied to any complex trait with distinct phenotypic subgroups.
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http://dx.doi.org/10.1002/gepi.22214DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6687557PMC
September 2019

Automated phone call and text reminders for childhood immunisations (PRIMM): a randomised controlled trial in Nigeria.

BMJ Glob Health 2019 3;4(2):e001232. Epub 2019 Apr 3.

Division of Infectious Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.

Background: Sub-Saharan Africa has high under-5 mortality and low childhood immunisation rates. Vaccine-preventable diseases cause one-third of under-5 deaths. Text messaging reminders improve immunisation completion in urban but not rural settings in sub-Saharan Africa. Low adult literacy may account for this difference. The feasibility and impact of combined automated voice and text reminders on immunisation completion in rural sub-Saharan Africa is unknown.

Methods: We randomised parturient women at the Mother and Child Hospitals Ondo State, Nigeria, owning a mobile phone and planning for child immunisation at these study sites to receive automated call and text immunisation reminders or standard care. We assessed the completion of the third pentavalent vaccine (Penta-3) at 18 weeks of age, immunisation completion at 12 months and within 1 week of recommended dates. We assessed selected demographic characteristics associated with completing immunisations at 12 months using a generalised binomial linear model with 'log' link function. Feasibility was assessed as proportion of reminders received.

Results: Each group had 300 mother-baby dyads with similar demographic characteristics. At 18 weeks, 257 (86%) and 244 (81%) (risk ratio (RR) 1.05, 95% CI 0.98 to 1.13; p=0.15) in the intervention and control groups received Penta-3 vaccine. At 12 months, 220 (74%) and 196 (66%) (RR 1.12, 95% CI 1.01 to 1.25; p=0.04) in the intervention and control groups received the measles vaccine. Infants in the intervention group were more likely to receive Penta-3 (84% vs 78%, RR 1.09, 95% CI 1.01 to 1.17; p=0.04), measles (73% vs 65%, RR 1.13, 95% CI 1.02 to 1.26; p=0.02) and all scheduled immunisations collectively (57% vs 47%, RR 1.13, 95% CI 1.02 to 1.26; p=0.01) within 1 week of the recommended date. No demographic character predicted immunisation completion. In the intervention group, 92% and 86% reported receiving a verification reminder and at least one reminder during the study period, respectively.

Conclusion: Paired automated call and text reminders significantly improved immunisation completion and timeliness.

Trial Registration Number: NCT02819895.
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http://dx.doi.org/10.1136/bmjgh-2018-001232DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6509606PMC
April 2019

Molecular Screening of VAX1 Gene Polymorphisms Uncovered the Genetic Heterogeneity of Nonsyndromic Orofacial Cleft Among Saudi Arabian Patients.

Genet Test Mol Biomarkers 2019 Jan;23(1):45-50

16 WHO Collaborating Centre, University of Dundee Dental School, Dundee, Scotland.

Objective: Nonsyndromic orofacial cleft (NSOFC) including cleft lip with or without cleft palate (CL±P) and cleft palate (CP) are multifactorial developmental disorders with both genetic and environmental etiological factors. In this study we investigated the association between CL±P and CP, and two polymorphisms previously determined using genome-wide association studies, as well as the association between consanguinity and CL±P and CP.

Methods: DNA was extracted from saliva specimens from 171 triads consisting of affected individuals and their parents, as well as 189 control triads (matched for age, gender, and location) that were recruited from 11 referral hospitals in Saudi Arabia. Two polymorphisms, rs4752028 and rs7078160, located in the VAX1 gene were genotyped using real-time polymerase chain reaction. A transmission disequilibrium test was carried out using the Family-Based Association Test and PLINK (genetic tool-set) to measure the parent-of-origin effect.

Results: Significant differences were found between affected individuals and the control group. In the case of the rs4752028 risk allele in cleft, the phenotypes were: CL±P (fathers: odds ratio [OR] 2.16 [95% CI 1.38-3.4]; mothers: OR 2.39 [95% CI 1.53-3.71]; and infants: OR 2.77 [95% CI 1.77-4.34]) and CP (fathers: OR 2.24 [95% CI 1.15-4.36] and infants: OR 2.43 [95% CI 1.25-4.7]). For CL±P and the rs7078160 risk allele, the phenotypes were: (fathers: OR 1.7 [95% CI 1.05-2.86]; mothers: OR 2.43 [95% CI 1.49-3.97]; and infants: OR 2.34 [95% CI 1.44-3.81]). In terms of consanguinity, we found significant association between consanguinity and the rs4752028 polymorphism minor allele among CL±P compared with controls (p = 0.001).

Conclusion: This is the first study to find a relationship between these two loci on 10q25 (rs4752028 and rs7078160) and NSOFC in a population with high levels of consanguinity.
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http://dx.doi.org/10.1089/gtmb.2018.0207DOI Listing
January 2019

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

Hum Mol Genet 2019 03;28(6):1038-1051

Center for Research on Genomics and Global Health, National Human Genome Research Institute, Bethesda, MD, USA.

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.
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http://dx.doi.org/10.1093/hmg/ddy402DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6400042PMC
March 2019

Genome-wide interaction studies identify sex-specific risk alleles for nonsyndromic orofacial clefts.

Genet Epidemiol 2018 10 11;42(7):664-672. Epub 2018 Sep 11.

Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, Georgia.

Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene-by-sex (G × S) interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls recruited from 13 countries. First, we performed genome-wide joint tests of the genetic (G) and G × S effects genome-wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test ( p < 1.00 × 10 ) by examining the G × S effects from the same model. Out of the 133 loci with suggestive results ( p < 1.00 × 10 ) for the joint test, we observed one genome-wide significant G × S effect in the 10q21 locus (rs72804706; p = 6.69 × 10 ; OR = 2.62 CI [1.89, 3.62]) and 16 suggestive G × S effects. At the intergenic 10q21 locus, the risk of NSCL/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. Our observation that the impact of genetic variants on NSCL/P risk differs for males and females may further our understanding of the genetic architecture of NSCL/P and the sex differences underlying clefts and other birth defects.
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http://dx.doi.org/10.1002/gepi.22158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185762PMC
October 2018

A comparative study of immediate wound healing complications following cleft lip repair using either absorbable or non-absorbable skin sutures.

J Korean Assoc Oral Maxillofac Surg 2018 Aug 29;44(4):159-166. Epub 2018 Aug 29.

Department of Oral and Maxillofacial Surgery, College of Medicine, University of Lagos, Lagos, Nigeria.

Objectives: The aim of the study was to compare wound healing complications following the use of either absorbable or non-absorbable sutures for skin closure in cleft lip repair.

Materials And Methods: This was a randomized controlled trial conducted at the Department of Oral and Maxillofacial Surgery, Lagos University Teaching Hospital, Idi Araba, Lagos State, Nigeria. Sixty subjects who required either primary or secondary cleft lip repair and satisfied all the inclusion criteria were recruited and randomized into two groups (Vicryl group or Nylon group). The surgical wounds in all subjects were examined on 3rd, 7th, and 14th postoperative days (POD) for presence or absence of tissue reactivity, wound dehiscence, and local wound infection.

Results: Hemorrhage, tissue reactivity, wound dehiscence, and local wound infection were identified as wound healing complications following cleft lip repair. The incidence of postoperative wound healing complications on POD3 was 33.3%. Tissue reactivity was more common throughout the evaluation period with the use of an absorbable (Vicryl) suture compared to a non-absorbable (Nylon) suture, although the difference was statistically significant only on POD7 (=0.002). There were no significant differences in the incidences of wound dehiscence and infection between the two groups throughout the observation period.

Conclusion: There were no statistically significant differences in the incidences of wound dehiscence and surgical site wound infection following the use of either Vicryl or Nylon for skin closure during cleft lip repair. However, more cases of tissue reactivity were recorded in the Vicryl group than in the Nylon group on POD7. Particular attention must be paid to detect the occurrence of wound healing complications, most especially tissue reactivity, whenever a Vicryl suture is used for skin closure in cleft lip repair.
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http://dx.doi.org/10.5125/jkaoms.2018.44.4.159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6117469PMC
August 2018

The dentist-scientist career pathway in Africa: opportunities and obstacles.

Korean J Med Educ 2018 Sep 27;30(3):189-198. Epub 2018 Aug 27.

Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA.

The future of evidence-based dentistry in developing Africa heavily depends on a sustainable establishment of a vibrant dentist-scientist workforce. A dentist scientist is saddled with the responsibility of carrying out robust cutting edge research projects that are inspired by clinical experience. Currently, there are no pipelines in place to systematically train such dentists, neither are there programs in place to allow trained African dentists choose such a career pathway. A dentist-scientist is a person who studied oral, dental, maxillofacial (or craniofacial) diseases, prevention, and population sciences (obtaining a medical degrees such as bachelor of dental surgery [BDS] or BChD) alone; or in combination with other advanced degrees such as doctor of dental surgery (DDS)/doctor of philosophy (PhD) or BDS/PhD. This situation has resulted in overdependence of African clinical practice on research findings from technologically advanced Western countries and a decline in clinical research capacity building. The career path of a dentist-scientist should involve research along the spectrum of basic biomedical sciences, translational, clinical and public health sciences. There are several factors responsible for the ultra-low count of dentist-scientist in the heterogeneous African communities such as: poor biomedical research infrastructure; lack of funding; absence of structured dentist scientist career pathways; lack of personnel, inter alia. Hence, this review hopes to discuss the opportunities of setting up a dentist-scientist training pathway in Africa (as obtains in most developed world settings), identify opportunities and prospects of developing an African dentist-scientist workforce, and finally discuss the challenges involved.
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http://dx.doi.org/10.3946/kjme.2018.93DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6127611PMC
September 2018

Identification of paternal uniparental disomy on chromosome 22 and a de novo deletion on chromosome 18 in individuals with orofacial clefts.

Mol Genet Genomic Med 2018 11 23;6(6):924-932. Epub 2018 Aug 23.

Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, Iowa.

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.
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http://dx.doi.org/10.1002/mgg3.459DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6305633PMC
November 2018

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

Oral Dis 2019 Jan 9;25(1):142-149. Epub 2018 Sep 9.

Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, University of the Western Cape and Tygerberg Hospital, Cape Town, South Africa.

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.
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http://dx.doi.org/10.1111/odi.12956DOI Listing
January 2019

Geriatric dentistry education and context in a selection of countries in 5 continents.

Spec Care Dentist 2018 May 30;38(3):123-132. Epub 2018 Mar 30.

Division of Dermatology, Department of Medicine, Faculty of Health Sciences and Groote Schuur Hospital, University of Cape Town, Cape Town, South Africa.

Purpose/aim: To summarize and discuss how geriatric dentistry has been addressed in dental schools of different countries regarding to (1) teaching students at the predoctoral level; (2) advanced training, and (3) research.

Method And Materials: A convenience sample of faculty members from a selection of high, upper-middle and lower-middle income countries were recruited to complete the survey. The survey had 5 open-ended main topics, and asked about (1) the size of their elderly population, (2) general information about dental education; (3) the number of dental schools teaching geriatric dentistry, and their teaching methods; (4) advanced training in geriatric dentistry; (5) scholarship/research in geriatric dentistry.

Results And Conclusion: (1) There is great variation in the size of elderly population; (2) duration of training and content of dental education curriculum varies; (3) geriatric dentistry has not been established as a standalone course in dental schools in the majority of the countries, (4) most countries, with the exception of Japan, lack adequate number of dentists trained in geriatric dentistry as well as training programs, and (5) geriatric dentistry-related research has increased in recent years in scope and content, although the majority of these papers are not in English.
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http://dx.doi.org/10.1111/scd.12281DOI Listing
May 2018

A multi-centre evaluation of oral cancer in Southern and Western Nigeria: an African oral pathology research consortium initiative.

Pan Afr Med J 2017 22;28:64. Epub 2017 Sep 22.

Department of Oral and Maxillofacial Pathology, Faculty of Dentistry, University of the Western Cape and Tygerberg Hospital, Cape Town, South Africa.

Introduction: Oral cancer is a leading cause of cancer deaths among African populations. Lack of standard cancer registries and under-reporting has inaccurately depicted its magnitude in Nigeria. Development of multi-centre collaborative oral pathology networks such as the African Oral Pathology Research Consortium (AOPRC) facilitates skill and expertise exchange and fosters a robust and systematic investigation of oral diseases across Africa.

Methods: In this descriptive cross-sectional study, we have leveraged the auspices of the AOPRC to examine the burden of oral cancer in Nigeria, using a multi-centre approach. Data from 4 major tertiary health institutions in Western and Southern Nigeria was generated using a standardized data extraction format and analysed using the SPSS data analysis software (version 20.0; SPSS Inc. Chicago, IL).

Results: Of the 162 cases examined across the 4 centres, we observed that oral squamous cell carcinomas (OSCC) occurred mostly in the 6 and 7 decades of life and maxillary were more frequent than mandibular OSCC lesions. Regional variations were observed both for location, age group and gender distribution. Significant regional differences was found between poorly, moderately and well differentiated OSCC (p value = 0.0071).

Conclusion: A multi-centre collaborative oral pathology research approach is an effective way to achieve better insight into the patterns and distribution of various oral diseases in men of African descent. The wider outlook for AOPRC is to employ similar approaches to drive intensive oral pathology research targeted at addressing the current morbidity and mortality of various oral diseases across Africa.
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http://dx.doi.org/10.11604/pamj.2017.28.64.13089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5873219PMC
April 2018

Oral Health-Related Quality of Life of Children Born With Orofacial Clefts in Ethiopia and Their Parents.

Cleft Palate Craniofac J 2018 Jan 1:1055665618760619. Epub 2018 Jan 1.

9 Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.

Objective: To assess the oral health-related quality of life (OH-RQoL) using a translated standardized measure in an understudied population of Ethiopian children born with orofacial clefts (OFCs) and their parents.

Methods: Using a descriptive study design, we assessed the OH-RQoL of 41 patients with OFCs between the ages of 8 and 17 years and their parents. Participants received multidisciplinary cleft care from 2008 to 2016. They completed an Amharic translation of the Child Oral Health Impact Profile (COHIP).

Results: There was strong internal reliability with the translated COHIP for parents and patients. Parents' COHIP scores ranged from 67 to 186, and patients' scores were 78 to 190. The mean for patients and parents was 155, indicating good OH-RQoL.

Conclusion: The Amharic translation of the COHIP appears appropriate for use with families in Ethiopia. Both parents and patients reported OH-RQoL at similar levels as other international populations.
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http://dx.doi.org/10.1177/1055665618760619DOI Listing
January 2018

Unilateral cleft lip repair: a comparison of treatment outcome with two surgical techniques using quantitative (anthropometry) assessment.

J Korean Assoc Oral Maxillofac Surg 2018 Feb 26;44(1):3-11. Epub 2018 Feb 26.

Department of Oral Pathology, Radiology, and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.

Objectives: The unilateral cleft lip (UCL) repair technique has evolved extensively over the past century into its modern form and has been identified as an important determinant of treatment outcome. The aim of this study was to evaluate and compare treatment outcomes following repair of UCL using either the Tennison-Randall (triangular) technique or the Millard rotation-advancement technique.

Materials And Methods: This was a prospective randomized controlled study conducted at the Lagos University Teaching Hospital between January 2013 and July 2014. A total of 48 subjects with UCL presenting for primary surgery and who satisfied the inclusion criteria were recruited for the study. The subjects were randomly allocated into two surgical groups through balloting. Group A underwent cleft repair with the Tennison-Randall technique, while group B underwent cleft repair with the Millard rotation-advancement technique. Surgical outcome was assessed quantitatively according to anthropometric measurements, using a method described by Cutting and Dayan (2003).

Results: Our 48 enrolled subjects were evenly divided into the two surgery groups (n=24 for both group A and group B). Twenty-seven subjects were male (56.3%) and 21 were female (43.8%), making a sex ratio of 1.3:1. The Millard group showed a greater increase in postoperative horizontal length and vertical lip height and a greater reduction in nasal width and total nasal width. Meanwhile, the Tennison-Randall group showed better reduction of Cupid's-bow width and better philtral height.

Conclusion: We did not find any significant differences in the surgical outcomes from the two techniques. The expertise of the surgeon and individual patient preferences are the main factors to consider when selecting the technique for unilateral cleft repair.
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http://dx.doi.org/10.5125/jkaoms.2018.44.1.3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5845966PMC
February 2018

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

Cleft Palate Craniofac J 2018 05 28;55(5):736-742. Epub 2018 Feb 28.

15 Department of Oral Pathology, Radiology and Medicine, University of Iowa, Iowa City, IA, USA.

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.
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http://dx.doi.org/10.1177/1055665618754948DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6081638PMC
May 2018

Identification of 16q21 as a modifier of nonsyndromic orofacial cleft phenotypes.

Genet Epidemiol 2017 12 10;41(8):887-897. Epub 2017 Nov 10.

Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, Georgia, United States of America.

Orofacial clefts (OFCs) are common, complex birth defects with extremely heterogeneous phenotypic presentations. Two common subtypes-cleft lip alone (CL) and CL plus cleft palate (CLP)-are typically grouped into a single phenotype for genetic analysis (i.e., CL with or without cleft palate, CL/P). However, mounting evidence suggests there may be unique underlying pathophysiology and/or genetic modifiers influencing expression of these two phenotypes. To this end, we performed a genome-wide scan for genetic modifiers by directly comparing 450 CL cases with 1,692 CLP cases from 18 recruitment sites across 13 countries from North America, Central or South America, Asia, Europe, and Africa. We identified a region on 16q21 that is strongly associated with different cleft type (P = 5.611 × 10 ). We also identified significant evidence of gene-gene interactions between this modifier locus and two recognized CL/P risk loci: 8q21 and 9q22 (FOXE1) (P = 0.012 and 0.023, respectively). Single nucleotide polymorphism (SNPs) in the 16q21 modifier locus demonstrated significant association with CL over CLP. The marker alleles on 16q21 that increased risk for CL were found at highest frequencies among individuals with a family history of CL (P = 0.003). Our results demonstrate the existence of modifiers for which type of OFC develops and suggest plausible elements responsible for phenotypic heterogeneity, further elucidating the complex genetic architecture of OFCs.
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http://dx.doi.org/10.1002/gepi.22090DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5728176PMC
December 2017

A comparative study of quality of life of families with children born with cleft lip and/or palate before and after surgical treatment.

J Korean Assoc Oral Maxillofac Surg 2017 Aug 24;43(4):247-255. Epub 2017 Aug 24.

Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa, Iowa City, IA, USA.

Objectives: The aim of this study was to compare the quality of life (QoL) of parents/caregivers of children with cleft lip and/or palate before and after surgical repair of an orofacial cleft.

Materials And Methods: Families of subjects who required either primary or secondary orofacial cleft repair who satisfied the inclusion criteria were recruited. A preoperative and postoperative health-related QoL questionnaire, the 'Impact on Family Scale' (IOFS), was applied in order to detect the subjectively perceived QoL in the affected family before and after surgical intervention. The mean pre- and postoperative total scores were compared using paired t-test. Pre- and postoperative mean scores were also compared across the 5 domains of the IOFS.

Results: The proportion of families whose QoL was affected before surgery was 95.7%. The domains with the greatest impact preoperatively were the financial domain and social domains. Families having children with bilateral cleft lip showed QoL effects mostly in the social domain and 'impact on sibling' domain. Postoperatively, the mean total QoL score was significantly lower than the mean preoperative QoL score, indicating significant improvement in QoL (<0.001). The mean postoperative QoL score was also significantly lower than the mean preoperative QoL score in all domains. Only 3.2% of the families reported affectation of their QoL after surgery. The domains of mastery (61.3%) with a mean of 7.4±1.8 and finance (45.1%) with a mean score of 7.2±1.6 were those showing the greatest postoperative impact. The proportion of families whose QoL was affected by orofacial cleft was markedly different after treatment (95.7% preoperative and 3.2% postoperative).

Conclusion: Caring for children with orofacial clefts significantly reduces the QoL of parents/caregivers in all domains. However, surgical intervention significantly improves the QoL of the parents/caregivers of these children.
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http://dx.doi.org/10.5125/jkaoms.2017.43.4.247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5583199PMC
August 2017