Genetic "Short Circuit" Leads To Cleft Palate

Scientists have identified not just a single gene but a genetic circuit, that when broken, causes cleft palate in newborn mice. The critical points of the circuit represent genes and gene products that interact with one another to direct palate formation. The "surge" that causes the circuit to break is an environmental assault in the form of steroid hormones given to the female mice during pregnancy. This is the first time that a cause-effect scenario for cleft palate has been worked out at the molecular level.

The findings may help define the genetic components of cleft palate in humans, and also explain the link between clefting and risk factors, such as stress, smoking, and certain medications, all of which are known to elevate the level of steroids in the body. The study was carried out by Drs. Michael Melnick, Tina Jaskoll, and colleagues at the University of Southern California through support from the National Institute of Dental Research, and appears in the January issue of Developmental Dynamics.

Facial clefting disorders are among the most common human birth defects. Cleft palate occurs in about one in 2,000 live births and can range in severity from a relatively minor split uvula at the rear of the mouth, to a cleft that runs the length of the hard and soft tissues that form the roof of the mouth. The more severe forms require surgery and are often associated with both psychological and physical problems, including difficulties with feeding, breathing, and speech development.

Cleft palate is thought to result from a combination of genetic and environmental factors, yet attempts to identify these components in human populations have so far produced inconclusive results. Investigators like Dr. Melnick feel that the mouse model will provide the clues that eventually unravel the mysteries of cleft palate. At present, he thinks that it is still premature to pinpoint the underlying causes of clef

Contact: Wayne Little
NIH/National Institute of Dental and Craniofacial Research

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