title: Novel IRF6 mutations in families with Van Der Woude syndrome and popliteal pterygium syndrome from sub-Saharan Africa.
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.
authors.affiliation: Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa Iowa City, Iowa.
authors.forename: Azeez
authors.initials: A
authors.lastname: Butali
authors.affiliation: Department of Orthodontics, University of Dundee Dundee, Scotland.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Mossey
authors.affiliation: College of Medicine, University of Lagos Lagos, Nigeria.
authors.forename: Wasiu L
authors.initials: WL
authors.lastname: Adeyemo
authors.affiliation: Addis Ababa University Addis Ababa, Ethiopia.
authors.forename: Mekonen A
authors.initials: MA
authors.lastname: Eshete
authors.affiliation: Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa Iowa City, Iowa.
authors.forename: LauRen A
authors.initials: LA
authors.lastname: Gaines
authors.affiliation: Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa Iowa City, Iowa.
authors.forename: Dee
authors.initials: D
authors.lastname: Even
authors.affiliation: Obafemi Awolowo University Ile-Ife, Nigeria.
authors.forename: Ramat O
authors.initials: RO
authors.lastname: Braimah
authors.affiliation: Obafemi Awolowo University Ile-Ife, Nigeria.
authors.forename: Babatunde S
authors.initials: BS
authors.lastname: Aregbesola
authors.affiliation: Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa Iowa City, Iowa.
authors.forename: Jennifer V
authors.initials: JV
authors.lastname: Rigdon
authors.affiliation: College of Medicine, University of Lagos Lagos, Nigeria.
authors.forename: Christian I
authors.initials: CI
authors.lastname: Emeka
authors.affiliation: College of Medicine, University of Lagos Lagos, Nigeria.
authors.forename: Olutayo
authors.initials: O
authors.lastname: James
authors.affiliation: College of Medicine, University of Lagos Lagos, Nigeria.
authors.forename: Mobolanle O
authors.initials: MO
authors.lastname: Ogunlewe
authors.affiliation: College of Medicine, University of Lagos Lagos, Nigeria.
authors.forename: Akinola L
authors.initials: AL
authors.lastname: Ladeinde
authors.affiliation: Addis Ababa University Addis Ababa, Ethiopia.
authors.forename: Fikre
authors.initials: F
authors.lastname: Abate
authors.affiliation: Addis Ababa University Addis Ababa, Ethiopia.
authors.forename: Taye
authors.initials: T
authors.lastname: Hailu
authors.affiliation: Addis Ababa University Addis Ababa, Ethiopia.
authors.forename: Ibrahim
authors.initials: I
authors.lastname: Mohammed
authors.affiliation: Addis Ababa University Addis Ababa, Ethiopia.
authors.forename: Paul E
authors.initials: PE
authors.lastname: Gravem
authors.affiliation: Addis Ababa University Addis Ababa, Ethiopia.
authors.forename: Milliard
authors.initials: M
authors.lastname: Deribew
authors.affiliation: Addis Ababa University Addis Ababa, Ethiopia.
authors.forename: Mulualem
authors.initials: M
authors.lastname: Gesses
authors.affiliation: Center for Research on Genomics and Global Health, National Human Genome Research Institute, National Institutes of Health Bethesda, Maryland.
authors.forename: Adebowale A
authors.initials: AA
authors.lastname: Adeyemo
authors.affiliation: Department of Oral Pathology, Radiology and Medicine, College of Dentistry, University of Iowa Iowa City, Iowa.
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
keywords: IRF6; Van der Woude syndrome; popliteal pterygium syndrome; sub-Saharan Africa