The authors say this latest gene test, when used with parents who already have one child with isolated cleft lip and palate, can predict this birth defect in subsequent children about 12 percent of the time. Utilizing this new gene test along with others that have already been developed, scientists now can collectively predict about 15 percent of isolated cleft lip and palate cases, impossible just a few years ago.

One of the first diagnostic tools of its kind, the gene test is based on distinct mutations in and around the gene IRF6, which encodes a specific protein that plays a vital role in the normal formation of the lips, palate, skin and genitalia during the early stages of development. The researchers found that mutations of the IRF6 gene are associated with an increased chance that a child would be born with a cleft lip or palate.

Two years ago, Murray and colleagues found that the IRF6 gene plays a role in Van der Woude Syndrome, a condition in which babies are born with clefts that are accompanied by other birth defects. There are more than 150 such syndromes, accounting for the remaining 30 percent of all cleft lip and palate.

Upon detailed analysis of the IRF6 gene, the researchers noticed a variation in the DNA sequence that they guessed may play a role in causing isolated clefts. The team reasoned the variation would somehow interfere with the normal biological activities of the IRF6 protein during tissue and organ development.

To test their hypothesis, the researchers focused their attention on a pool of 1,968 families, in Europe, South America, and Asia, with a history of isolated clefts. According to Murray, the rate of isolated clefts in some parts of the world, such as the Philippines, Brazil, and China, is even higher than in th
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Contact: John Peterson
peterso4@niehs.nih.gov
919-541-7860
NIH/National Institute of Environmental Health Sciences
10-Sep-2004