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Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub‐Saharan Africa
Journal article   Open access   Peer reviewed

Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub‐Saharan Africa

Azeez Butali, Peter A Mossey, Wasiu L Adeyemo, Mekonen A Eshete, LauRen A Gaines, Dee Even, Ramat O Braimah, Babatunde S Aregbesola, Jennifer V Rigdon, Christian I Emeka, …
Molecular genetics & genomic medicine, Vol.2(3), pp.254-260
05/2014
DOI: 10.1002/mgg3.66
PMCID: PMC4049366
PMID: 24936515
url
https://doi.org/10.1002/mgg3.66View
Published (Version of record) Open Access

Abstract

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 IRF6 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 IRF6 (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 IRF6‐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. IRF6 mutations in two African populations with Van Der Woude and Popliteal Pterygium Syndrome. This will be valuable knowledge for genetic counseling in a region with limited expertise.
sub‐Saharan Africa Van der Woude syndrome IRF6 popliteal pterygium syndrome

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