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

Azeez Butali (Lead / Corresponding author), 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, Olutayo James, Mobolanle O. Ogunlewe, Akinola L. Ladeinde, Fikre Abate, Taye Hailu, Ibrahim Mohammed, Paul E. Gravem, Milliard Deribew, Mulualem Gesses, Adebowale A. AdeyemoJeffrey C. Murray

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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.
Original languageEnglish
Pages (from-to)254-260
Number of pages7
JournalMolecular Genetics and Genomic Medicine
Volume2
Issue number3
Early online date27 Jan 2014
DOIs
Publication statusPublished - May 2014

Keywords

  • IRF6
  • popliteal
  • pterygium syndrome
  • sub-Saharan Africa
  • Van der Woude syndrome

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    • Dentistry - Professor (Clinical) & Personal Chair of Craniofacial Dev & Dentofacial Orthopaeds

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    Butali, A., Mossey, P. A., Adeyemo, W. L., Eshete, M. A., Gaines, L. A., Even, D., Braimah, R. O., Aregbesola, B. S., Rigdon, J. V., Emeka, C. I., James, O., Ogunlewe, M. O., Ladeinde, A. L., Abate, F., Hailu, T., Mohammed, I., Gravem, P. E., Deribew, M., Gesses, M., ... Murray, J. C. (2014). Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub-Saharan Africa. Molecular Genetics and Genomic Medicine, 2(3), 254-260. https://doi.org/10.1002/mgg3.66