For the first time, researchers from the University of Pittsburgh School of Dental Medicine have identified a series of genetic mutations that appear to be linked to significant risk for cleft palate and other dental abnormalities. These are devastating conditions that cause tremendous social isolation, and also are associated with decreased lifespan, a higher risk of cancer and increased susceptibility to psychiatric disorders, even after surgical repair. As reported in the September issue of Genetics in Medicine, Alexandre Vieira, DDS, Ph.D., assistant professor in the Department of Oral Biology, University of Pittsburgh School of Dental Medicine, and colleagues collected and evaluated genetic material from the saliva and blood of more than 500 individuals in family groups with two or more siblings affected with cleft lip or palate, and an additional 100 people from unrelated families whose samples were used for general-population comparison data.
University of Iowa researchers and collaborators have found, in a previously identified gene, a variation that likely contributes to one in five cases of isolated cleft lip. It is the first time a genetic variant has been associated with cleft lip alone, rather than both cleft lip and palate. The study provides insight on a previously unknown genetic mechanism and could eventually help with diagnosis, prevention and treatment of cleft lip, which affects more than five million people worldwide. The findings appeared Oct. 5 in the journal Nature Genetics. In 2004, a worldwide team involving the University of Iowa identified the gene IRF6 as a contributor to about 12 percent of cases of the common form of cleft lip and palate. The new finding pinpoints a regulatory part of the IRF6 gene that binds to a protein called AP2.
Babies whose mothers smoked during pregnancy were more than twice as likely to have a cleft palate or lip as those whose mothers didn't, according to research results released today. Although the study confirms earlier findings, it is unique because it did not rely on women's self-reported smoking habits during pregnancy. Instead, researchers used the more reliable method of measuring the levels of cotinine, a metabolite of nicotine, in the blood from about 500 pregnant women. "This research is the first time we've been able to measure something - in this case cotinine - and determine the risk of smoking during pregnancy for oral-facial birth defects, " Gary M. Shaw, PhD, research director and senior epidemiologist of the March of Dimes California Research Division, Children's Hospital Oakland Research Institute in Oakland, Calif.
Smoking during the first trimester of pregnancy is clearly linked with an increased risk of cleft lip in newborns. Genes that play a role in detoxification of cigarette smoke do not appear to be involved. This is shown in a new study published in the journal Epidemiology. Oral clefts are one of the most common birth defects. Closure of the lip occurs about 5 weeks into pregnancy, followed by closure of the palate at week 9. If this does not happen, a cleft lip and/or cleft palate are the result, requiring surgery. The researchers wanted to see if smoking or exposure to passive smoking play a role in these defects and whether genes influence the oral cleft risk through the way toxic chemicals in cigarette smoke are processed. The study is based on an extensive Norwegian case-control study on oral clefts with collaborating researchers from the Norwegian Institute of Public Health, University of Bergen, Rikshospital, Haukeland University Hospital and the National Institutes of Health in USA.
Study Of Changes In MSX Gene Family Over 600 Million Years Leads To New Understanding Of Disease Patterns
The work of Forsyth scientist Peter Jezewski, DDS, Ph.D., has revealed that duplication and diversification of protein regions ('modules') within ancient master control genes is key to the understanding of certain birth disorders. Tracing the history of these changes within the proteins coded by the Msx gene family over the past 600 million years has also provided additional evidence for the ancient origin of the human mouth. Dr. Jezewski has published an important study examining the Msx family that has ancient roots as a master control gene for patterned embryonic growth. Previous work by Dr. Jezewski, and other groups, identified mutations within the human MSX1 gene in two different birth disorders: either cleft lip and palate or skin derivative disorders ('ectodermal dysplasias') that include tooth and nail malformations.