Journal article
The prevalence, penetrance, and expressivity of etiologic IRF6 variants in orofacial clefts patients from sub‐Saharan Africa
Molecular genetics & genomic medicine, Vol.5(2), pp.164-171
03/2017
DOI: 10.1002/mgg3.273
PMCID: PMC5370218
PMID: 28361103
Abstract
Background
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.
This is a study on orofacial clefts from three African populations. We have shown evidence of pathogenic variants in our cohort.
Details
- Title: Subtitle
- The prevalence, penetrance, and expressivity of etiologic IRF6 variants in orofacial clefts patients from sub‐Saharan Africa
- Creators
- Lord Jephthah Joojo Gowans - University of IowaTamara D Busch - University of IowaPeter A Mossey - University of DundeeMekonen A Eshete - Addis Ababa UniversityWasiu L Adeyemo - University of LagosBabatunde Aregbesola - Obafemi Awolowo University Teaching HospitalPeter Donkor - KNUSTFareed K. N Arthur - Kwame Nkrumah University of Science and Technology (KNUST)Pius Agbenorku - KNUSTJames Olutayo - University of LagosPeter Twumasi - Kwame Nkrumah University of Science and Technology (KNUST)Rahman Braimah - Obafemi Awolowo University Teaching HospitalAlexander A Oti - KNUSTGyikua Plange‐Rhule - Komfo Anokye Teaching HospitalSolomon Obiri‐Yeboah - KNUSTFikre Abate - Addis Ababa UniversityPaa E Hoyte‐Williams - Komfo Anokye Teaching HospitalTaye Hailu - Addis Ababa UniversityJeffrey C Murray - University of IowaAzeez Butali - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Molecular genetics & genomic medicine, Vol.5(2), pp.164-171
- DOI
- 10.1002/mgg3.273
- PMID
- 28361103
- PMCID
- PMC5370218
- NLM abbreviation
- Mol Genet Genomic Med
- ISSN
- 2324-9269
- eISSN
- 2324-9269
- Number of pages
- 8
- Grant note
- Robert Wood Johnson Foundation (72429) NIH R37 (DE‐08559; DE‐016148) NIDCR K99/R00 (DE022378‐03) The Ghana Cleft Foundation
- Language
- English
- Date published
- 03/2017
- Academic Unit
- Oral Pathology, Radiology and Medicine; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025450802771
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