EAST LANSING, Mich. – Cleft lip and cleft palate are some of the most common birth defects in people, affecting roughly one in every 700 babies in the world. Cleft lip — when the upper lip is split — is more common than cleft palate — when the roof of the mouth (palate) is split — except in Finland, where cases of cleft palate are so common they flip the ratio of cleft lip to cleft palate.
Researchers have identified a likely culprit: a change in DNA variant near a specific gene. Previous studies showed that DNA changes in this gene cause and contribute to risk for both cleft lip and cleft palate. Surprisingly, in this new study, published in Nature Communications, researchers found the effect of this DNA variant only increases risk for cleft palate.
Brian Schutte, geneticist, associate professor and co-director of the D.O.-Ph.D. Physician-Scientist Training Program at the MSU College of Osteopathic Medicine, along with scientists from FinnGen, AbbVie Inc., the University of Helsinki, the University of Washington School of Dentistry, the Estonian Genome Center and other key collaborators, tie this change in DNA, which is found only in Finland and Estonia, to Finland’s high frequency of cleft palate. The team also connects this DNA change to Finland’s statistically significant geographic distribution of cleft palate cases, which become more frequent from the southwest to the northeast. This regional distribution of cleft palate has not been observed anywhere else in the world.
In next steps, Schutte will work with the Michigan Department of Health and Human Services to genotype blood samples from Michigan’s BioTrust. These samples will come from babies born with cleft palates from Ontonagon, Houghton, Schoolcraft, Marquette and Chippewa counties, where a significant number of Michiganders with Finnish ancestry live.
“If we find the DNA change in those Michigan samples, but the frequency of cleft palate is not high like it is in Finland, that would suggest an environmental or other component that makes cleft palate less common in Michigan than in Finland, despite the genetic connection between the people,” Schutte said. “That has clinical, risk and public health ramifications.”