University of Iowa researchers and collaborators have identified new genetic mutations that likely cause the common form of cleft lip and palate
The results could eventually help clinicians predict a family's risk of having more children with the condition. The findings appear in the week of March 5 online Early Edition of the Proceedings of the National Academy of Sciences.
Cleft lip and palate, found in nearly one of every 700 live births worldwide, occurs when tissues that normally form the lip and palate fail to join early in fetal life. The investigation focused on genes in the fibroblast growth factor (FGF) family, which function in a signaling pathway important in fetal face development, said Bridget Riley, a student in the UI Genetics Ph.D. Program and the study's primary author.
"The fibroblast growth factor signaling pathway is interesting because it is involved in many developmental processes, and we were especially interested in how it affects facial development. Prior to this study, the fibroblast growth factors had been looked at in syndromic forms of clefting but had not been examined in non-syndromic forms," said Riley, whose research team is based in the lab of Jeff Murray, M.D., a professor with multiple UI appointments and a study co-author.
The common form of cleft lip and palate is also known as non-syndromic, as it occurs in isolation and not in association with any known syndrome. The team compared the DNA from 184 people from Iowa and the Philippines had non-syndromic cleft lip and palate with DNA from people without the condition. Riley led the effort that found the mutations in FGF ligands and associated receptors.
Computer modeling of proteins, completed by Moosa Mohammadi, Ph.D., associate professor of pharmacology at New York University School of Medicine, indicated that each mutation would disrupt FGF signaling in a different way. The team will next test the mutant proteins to see if
Contact: Becky Soglin
University of Iowa