Genetic studies in the nigerian population implicate an MSX1 mutation in complex oral facial clefting disorders

BACKGROUND: Orofacial clefts are the most common malformations of the head and neck with a World-wide prevalence of 1/700 births. They are commonly divided into CL(P) and CP based on anatomical, genetic and embryological findings. A Nigerian craniofacial anomalies study “NigeriaCRAN” was set up in 2006 to investigate the role of gene-environment interaction in the etiology of orofacial clefts in Nigeria. SUBJECTS AND METHODS: DNA isolated from saliva from the Nigerian probands was used for genotype association studies and direct sequencing on the cleft candidate genes: MSX1, IRF6, FOXE1, FGFR1, FGFR2, BMP4, MAFB, ABCA4, PAX7 and VAX1, and the chromosome 8q region. RESULTS: A missense mutation A34G in MSX1 was observed in nine cases and four hap map controls. No other apparent etiologic variations were identified. A deviation from HWE was observed in the cases (p= 0.00002). There was a significant difference between the affected side for unilateral CL (p=0.03) and, between bilateral clefts and clefts on either side (p=0.02). A significant gender difference was also observed for CP (p=0.008). CONCLUSIONS: The replication of a mutation previously implicated in other populations suggests a role for the MSX1 A34G variant in the etiology of CL(P)