A consortium of scientists supported by the National Institutes of Health has identified 2 human genes that, when inherited in a slightly altered form, may play a role in causing cleft lip and/or palate, one of the world’s most common congenital malformations. Using the largest genome-wide association study to date on cleft lip and/or palate allowed researchers to survey the DNA of people with a shared condition to measure hundreds of thousands of different points across the genome that can be indicative of a nearby gene alteration. By working as a consortium and through the consent of more than 1,900 affected families from 8 countries, they were able to detect variations close to genes called MAFB and ABCA4. The variations suggest that altered forms of these genes may be related to clefting. The discoveries were independently replicated by studying 1,965 more affected families from 12 countries, or a total of 8,115 people. Researchers later obtained additional DNA from participants born with a cleft, sequenced portions of the MAFB and ABCA4 genes, and identified protein-altering changes in some of these samples. They also found in studies with mice that MAFB is expressed early in the development of the head and face, including during the fusion of the roof of the mouth, an indication the MAFB protein is needed for the normal development of the palate. They also confirmed that the previously identified gene IRF6 and a suspected segment of chromosome 8 seem to be frequently altered in people born with clefts. About 70% of babies born with a cleft lip and/or palate have the isolated form and no other associated birth defects. Among whites, isolated clefts occur in an estimated one in every 1,000 live births. The frequency seems to be even higher in some Asian countries, ie, China and the Philippines, but lower among people of African descent.
(Source: National Institute of Dental and Craniofacial Research news release, May 3, 2010)