Browsing Faculty of Dental Sciences by Author "Abdur-Rahman, L.O."
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- ItemOpen AccessGenetic studies in the Nigerian population implicate an MSX1 mutation in complex oral facial clefting disorders(SAGE JOURNALS, 2011-11-01) Butali, A.; Mossey, P.A.; Adeyemo, W.L.; Jezewski, P.A.; Onwuamah, C.K.; Ogunlewe, M.O.; Ugboko, V.I.; Adejuyigbe, O.; Adigun, A.I.; Abdur-Rahman, L.O.; Onah, I.I.; Audu, R.A.; Idigbe, E.O.; Mansilla, M.A.; Dragan, E.A.; Petrin, A.L.; Bullard, S.A.; Uduezue, A.O.; Akpata, O.; Osaguona, A.O.; Olasoji, H.O.; Ligali, T.O.; Kejeh, B.M.; Iseh, K.R.; Olaitan, P.B.; Adebola, A.R.; Efunkoya, E.; Adesina, O.A.; Oluwatosin, O.M.; Murray, J.C.BACKGROUND: Orofacial clefts are the most common malformations of the head and neck, with a worldwide prevalence of 1 in 700 births. They are commonly divided into CL(P) and CP based on anatomic, genetic, and embryologic findings. A Nigerian craniofacial anomalies study (NigeriaCRAN) was set up in 2006 to investigate the role of gene-environment interaction in the origin of orofacial clefts in Nigeria. SUBJECTS AND METHODS: DNA isolated from saliva from Nigerian probands was used for genotype association studies and direct sequencing of cleft candidate genes: MSX1 , IRF6 , FOXE1, FGFR1 , FGFR2 , BMP4 , MAFB, ABCA4 , PAX7, and VAX1 , and the chromosome 8q region. RESULTS: A missense mutation A34G in MSX1 was observed in nine cases and four HapMap controls. No other apparent causative variations were identified. Deviation from Hardy Weinberg equilibrium (HWE) was observed in these cases (p = .00002). A significant difference was noted between the affected side for unilateral CL (p = .03) and bilateral clefts and between clefts on either side (p = .02). A significant gender difference was also observed for CP (p = .008). CONCLUSIONS: Replication of a mutation previously implicated in other populations suggests a role for the MSX1 A34G variant in the development of CL(P).
- ItemOpen AccessGenomic analyses in African populations identify loci for cleft palate(Oxford Academic, 2019-03-15) Butali, A.; Mossey, P.A.; Adeyemo, W.L.; Eshete, M.A.; Gowans, L.J.J.; Busch, T.; Jain, D.; Yu, W.; Huan, L.; Laurie, C.C.; Laurie, C.A.; Nelson, S.; Li, M.; Sanchez-Lara, P.A.; Magee, W.P.; Magee, K.S.; Auslander, A.; Brindopke, F.; Kay, D.M.; Caggana, M.; Romitti, P.A.; Mills, J.L.; Audu, R.; Onwuamah, C.; Oseni, G.O.; Owais, A.; James, O.; Olaitan, P.B.; Aregbesola, B.S.; Braimah, R.O.; Oginni, F.O.; Oladele, A.O.; Bello, S.A.; Rhodes, J.; Shiang, R.; Donkor, P.; Obiri-Yeboah, S.; Arthur, F.K.N.; Twumasi, P.; Agbenorku, P.; Plange-Rhule, G.; Oti, A.; Ogunlewe, M.O.; Oladega, A.A.; Adekunle, A.A.; Erinoso, A.O.; Adamson, O.O.; Elufowoju, A.A.; Ayelomi, O.I.; Hailu, T.; Hailu, A.; Demissie, Y.; Derebew, M.; Eliason, S.; Romero-Bustillous, M.; Lo, C.; Park, J.; Desai, S.; Mohammed, M.; Abate, F.; Abdur-Rahman, L.O.; Anand, D.; Saadi, I.; Oladugba, A.V.; Lachke, S.A.; Amendt, B.A.; Rotimi, C.N.; Marazita, M.L.; Cornell, R.A.; Murray, J.C.; Adeyemo, A.A.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.
- ItemOpen AccessIdentification of paternal uniparental disomy on chromosome 22 and a de novo deletion on chromosome 18 in individuals with orofacial clefts(Wiley, 2018-11-01) Oseni, G.O.; Jain, D.; Mossey, P.A.; Busch, T.D.; Gowans, L.J.J.; Eshete, M.A.; Adeyemo, W.L.; Laurie, C.A.; Laurie, C.C.; Owais, A.; Olaitan, P.B.; Aregbesola, B.S.; Oginni, F.O.; Bello, S.A.; Donkor, P.; Audu, R.; Onwuamah, C.; Obiri-Yeboah, S.; Plange-Rhule, G.; Ogunlewe, M.O.; James, O.; Hailu, T.; Abate, F.; Abdur-Rahman, L.O.; Oladugba, A.V.; Marazita, M.L.; Murray, J.C.; Adeyemo, A.A.; Butali, A.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.
- ItemOpen AccessNovel GREM1 Variations in Sub-Saharan African Patients With Cleft Lip and/or Cleft Palate(SAGE JOURNALS, 2018-05-01) Gowans, L.J.J.; Oseni, G.; Mossey, P.A.; Adeyemo, W.L.; Eshete, M.A.; Busch, T.D.; Donkor, P.; Obiri-Yeboah, S.; Plange-Rhule, G.; Oti, A.A.; Owais, A.; Olaitan, P.B.; Aregbesola, B.S.; Oginni, F.O.; Bello, S.A.; Audu, R.; Onwuamah, C.; Agbenorku, P.; Ogunlewe, M.O.; Abdur-Rahman, L.O.; Marazita, M.L.; Adeyemo, A.A.; Murray, J.C.; Butali, A.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.