Open AccessNovel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub‐Saharan Africa
Author(s) -
Butali Azeez,
Mossey Peter A.,
Adeyemo Wasiu L.,
Eshete Mekonen A.,
Gaines LauRen A.,
Even Dee,
Braimah Ramat O.,
Aregbesola Babatunde S.,
Rigdon Jennifer V.,
Emeka Christian I.,
James Olutayo,
Ogunlewe Mobolanle O.,
Ladeinde Akinola L.,
Abate Fikre,
Hailu Taye,
Mohammed Ibrahim,
Gravem Paul E.,
Deribew Milliard,
Gesses Mulualem,
Adeyemo Adebowale A.,
Murray Jeffrey C.
Publication year - 2014
Publication title -
molecular genetics and genomic medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.765
H-Index - 29
ISSN - 2324-9269
DOI - 10.1002/mgg3.66
Subject(s) - missense mutation , exon , genetics , sanger sequencing , omim : online mendelian inheritance in man , genetic counseling , nonsense mutation , exon skipping , biology , gene , medicine , mutation , alternative splicing , phenotype
Orofacial clefts ( OFC ) are complex genetic traits that are often classified as syndromic or nonsyndromic clefts. Currently, there are over 500 types of syndromic clefts in the Online Mendelian Inheritance in Man ( OMIM ) database, of which Van der Woude syndrome ( VWS ) is one of the most common (accounting for 2% of all OFC ). Popliteal pterygium syndrome ( PPS ) is considered to be a more severe form of VWS . Mutations in the IRF 6 gene have been reported worldwide to cause VWS and PPS . Here, we report studies of families with VWS and PPS in sub‐Saharan Africa. We screened the DNA of eight families with VWS and one family with PPS from Nigeria and Ethiopia by Sanger sequencing of the most commonly affected exons in IRF 6 (exons 3, 4, 7, and 9). For the VWS families, we found a novel nonsense variant in exon 4 (p.Lys66X), a novel splice‐site variant in exon 4 (p.Pro126Pro), a novel missense variant in exon 4 (p.Phe230Leu), a previously reported splice‐site variant in exon 7 that changes the acceptor splice site, and a known missense variant in exon 7 (p.Leu251Pro). A previously known missense variant was found in exon 4 (p.Arg84His) in the PPS family. All the mutations segregate in the families. Our data confirm the presence of IRF 6 ‐related VWS and PPS in sub‐Saharan Africa and highlights the importance of screening for novel mutations in known genes when studying diverse global populations. This is important for counseling and prenatal diagnosis for high‐risk families.