Researchers Discover Gene for Common Form of Cleft Lip and Palate

FOR IMMEDIATE RELEASESeptember 20, 2001

Contact: George Carnes, (303) 315-5571

CU Researchers Discover Gene for Common Form of Cleft Lip and Palate

A major genetic discovery at the University of Colorado Health Sciences Center may lead eventually to the prevention of cleft lip and cleft palate (CL/P). Scientists at the CU-Colorado Health Sciences Center have pinpointed a gene involved in the most common form of CL/P. In an article published in the October issue of Nature Genetics, the researchers show a link between a mutation of a specific gene and the occurrence of CL/P. CL/P is one of the most frequently occurring of all birth defects, appearing in about one in every 500 births.

Working with collaborators in California and Venezuela, Richard Spritz, MD, director of the Human Medical Genetics Program at the CU-Health Sciences Center and principal investigator of the study, studied patients located in northern Venezuela, who have the common (or "sporadic") form of cleft lip and palate. Spritz and his colleagues found that many had a mutation of the gene, PVRL1. This is the first unequivocal identification of a gene involved in this most common form of CL/P.

This discovery builds on earlier research by the same team, which found that the same mutation in PVRL1 causes a rare inherited form of cleft lip and palate. "This is exciting news," said Spritz. "We have forged yet another link in a chain that we hope will eventually lead to better counseling and planning for at-risk couples, and ultimately to prevention of cleft lip and palate altogether."

Research on common birth defects such as CL/P has proved difficult; while the condition is common, there are relatively few families with many members with CL/P. Spritz's team approached the problem by first studying a rare form of CL/P in an isolated island population, and identified PVRL1 gene mutations in those patients. In the study reported in October's Nature Genetics, the team examined the incidence of PVRL1 mutation in patients with the far more common "sporadic" variety of CL/P.

Evidence from the study indicates that environmental factors are also at work. "The occurrence of CL/P appears to result from a combination of genes and environmental factors," Dr. Spritz said. "This birth defect is more prevalent in economically developing populations than in more affluent societies, and work needs to go forward to help us discover why this is the case."

"In the next phase of the study, we will look at patients with CL/P from throughout the United States. This work has already started, and initial results appear promising," Dr. Spritz added.

Cleft lip and/or palate occurs when structures around the mouth fail to grow together properly during early fetal development. Some cases of CL/P occur in combination with other abnormalities and may be inherited, but most cases of CL/P occur "sporadically", in individuals with no other problems and with no family history of the disease. The current study addresses this latter form of the disease.

The CL/P study is funded, in part, by a grant from the National Institutes of Health.

The University of Colorado Health Sciences Center is one of four campuses in the University of Colorado system. Located in Denver and Aurora, Colo., the center includes schools of medicine, nursing, pharmacy, and dentistry, a graduate school and two hospitals.

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