Research Articles >
College of Science >
Please use this identifier to cite or link to this item:
|Title: ||The prevalence, penetrance, and expressivity of etiologic IRF6 variants in orofacial clefts patients from sub-Saharan Africa|
|Authors: ||Gowans, Lord Jephthah Joojo|
Busch, Tamara D.
Mossey, Peter A.
Eshete, Mekonen A.
Adeyemo, Wasiu L.
Arthur, Fareed K. N.
Oti, Alexander A.
Abate, Fikre Abate
Hoyte-Williams, Paa E.
Murray, Jeffrey C.
|Keywords: ||Craniofacial genetics|
Van der Woude syndrome
|Issue Date: ||2017|
|Publisher: ||Molecular Genetics & Genomic Medicine|
|Citation: ||Molecular Genetics & Genomic Medicine 2017; 5(2): 164–171; doi: 10.1002/mgg3.273|
|Abstract: ||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.
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 50 and 30 untranslated regions. In our analyses pipeline, we used various
bioinformatics tools to detect and describe the potentially etiologic variants.
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.
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.|
|Description: ||An article published by Molecular Genetics & Genomic Medicine 2017; 5(2): 164–171; doi: 10.1002/mgg3.273|
|Appears in Collections:||College of Science|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.