Mutations Linked to Cleft Lip and Palate

Seven mutations in FGF pathway may account for up to 5 percent of cases

THURSDAY, March 8 (HealthDay News) -- Mutations in the fibroblast growth factor (FGF) signaling pathway, previously shown to be important in craniofacial development, can lead to cleft lip and palate, according to a report published online March 6 in the Proceedings of the National Academy of Sciences.

Jeffrey C. Murray, Ph.D., of the University of Iowa in Iowa City, and colleagues sequenced the coding regions and performed association testing on 12 genes in the FGF signaling pathway from 184 individuals with non-syndromic cleft lip and palate. Protein structural analysis was used to predict the functional consequences of amino acid variations.

The investigators identified seven different mutations that correlated with cleft lip and palate. The mutations may account for 3 percent to 5 percent of the disease cases. Each different mutation was predicted to disrupt FGF signaling, although by different mechanisms. Genetic mapping identified associations between single-nucleotide polymorphism in some of the FGF genes and cleft lip and palate.

"Clinically, we can begin to think about creating sequencing screening panels by using the FGF and FGFR genes as well as other candidate genes…which are highly likely to contribute to clefting," the authors write. "The technology and high-throughput nature of this method will allow physicians and genetic counselors to test for mutations in known causative genes and enable carrier detection, prenatal screening, and improved recurrence risk estimates for other family members."

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