The prevalence, penetrance, and expressivity of etiologic IRF6 variants in orofacial clefts patients from sub-Saharan Africa

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dc.contributor.authorGowans, L.J.J.
dc.contributor.authorBusch, T.D.
dc.contributor.authorMossey, P.A.
dc.contributor.authorEshete, M.A.
dc.contributor.authorAdeyemo, W.L.
dc.contributor.authorAregbesola, B.
dc.contributor.authorDonkor, P.
dc.contributor.authorArthur, F.K.
dc.contributor.authorAgbenorku, P.
dc.contributor.authorJames, O.
dc.contributor.authorTwumasi, P.
dc.contributor.authorBraimah, R.
dc.contributor.authorOti, A.A.
dc.contributor.authorPlange-Rhule, G.
dc.contributor.authorObiri-Yeboah, S.
dc.contributor.authorAbate, F.
dc.contributor.authorHoyte-Williams, P.E.
dc.contributor.authorHailu, T.
dc.contributor.authorMurray, J.C.
dc.contributor.authorButali, A.
dc.date.accessioned2019-10-31T08:47:12Z
dc.date.available2019-10-31T08:47:12Z
dc.date.issued2017-01-01
dc.descriptionStaff publicationsen_US
dc.description.abstractBACKGROUND: Orofacial clefts are congenital malformations of the orofacial region, with a global incidence of one per 700 live births. Interferon Regulatory Factor 6 (IRF6) (OMIM:607199) gene has been associated with the etiology of both syndromic and nonsyndromic orofacial clefts. The aim of this study was to show evidence of potentially pathogenic variants in IRF6 in orofacial clefts cohorts from Africa. METHODS: We carried out Sanger Sequencing on DNA from 184 patients with nonsyndromic orofacial clefts and 80 individuals with multiple congenital anomalies that presented with orofacial clefts. We sequenced all the nine exons of IRF6 as well as the 5' and 3' untranslated regions. In our analyses pipeline, we used various bioinformatics tools to detect and describe the potentially etiologic variants. RESULTS: We observed that potentially etiologic exonic and splice site variants were nonrandomly distributed among the nine exons of IRF6, with 92% of these variants occurring in exons 4 and 7. Novel variants were also observed in both nonsyndromic orofacial clefts (p.Glu69Lys, p.Asn185Thr, c.175-2A>C and c.1060+26C>T) and multiple congenital anomalies (p.Gly65Val, p.Lys320Asn and c.379+1G>T) patients. Our data also show evidence of compound heterozygotes that may modify phenotypes that emanate from IRF6 variants. CONCLUSIONS: This study demonstrates that exons 4 and 7 of IRF6 are mutational 'hotspots' in our cohort and that IRF6 mutants-induced orofacial clefts may be prevalent in the Africa population, however, with variable penetrance and expressivity. These observations are relevant for detection of high-risk families as well as genetic counseling. In conclusion, we have shown that there may be a need to combine both molecular and clinical evidence in the grouping of orofacial clefts into syndromic and nonsyndromic forms.en_US
dc.identifier.citationGowans LJ, Busch TD, Mossey PA, Eshete MA, Adeyemo WL, Aregbesola B, Donkor P, Arthur FK, Agbenorku P, Olutayo J, Twumasi P, Braimah R, Oti AA, Plange-Rhule G, Obiri-Yeboah S, Abate F, Hoyte-Williams PE, Hailu T, Murray JC, Butali A. The prevalence, penetrance, and expressivity of etiologic IRF6 variants in orofacial clefts patients from sub-Saharan Africa. Mol Genet Genomic Med. 2017 Jan 12;5(2):164-171.en_US
dc.identifier.urihttps://ir.unilag.edu.ng/handle/123456789/6625
dc.language.isoenen_US
dc.publisherWileyen_US
dc.relation.ispartofseriesMol Genet Genomic Med.;Vol.5(2)
dc.subjectVan der Woude syndromeen_US
dc.subjectCraniofacial geneticsen_US
dc.subjectPenetranceen_US
dc.subjectRare variantsen_US
dc.subjectPopulation geneticsen_US
dc.subjectResearch Subject Categories::ODONTOLOGYen_US
dc.titleThe prevalence, penetrance, and expressivity of etiologic IRF6 variants in orofacial clefts patients from sub-Saharan Africaen_US
dc.typeArticleen_US
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