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Gene Plays Key Role in Clubfoot
Date:10/27/2008

Finding could lead to tests, therapies, experts say

MONDAY, Oct. 27 (HealthDay News) -- The first gene linked to clubfoot has been identified by researchers at the Washington University School of Medicine in St. Louis, who analyzed the DNA of 35 extended family members of a male infant with clubfoot.

Through their analysis, the study authors concluded that a mutation in a gene called PITX1 -- which is critical for early development of lower limbs -- was responsible for the condition. The mutation was found in all 13 affected family members and in three carriers who showed no clinical symptoms.

Other genes may also play a role in clubfoot, but this finding is an initial step toward improved genetic counseling and the development of new therapies, the researchers said. The study appears in the Nov. 7 issue of the American Journal of Human Genetics.

"To our knowledge this report is the first evidence for PITX1 mutation in human disease," Dr. Christina Gurnett, an assistant professor of neurology, of pediatrics and of orthopedic surgery, said in a university news release. "Once we identified the mutation, we proved that all of the individuals in this family with lower extremity malformations also have the mutation. Having large families to work with is very helpful in genetic research."

Clubfoot, which affects about one in 1,000 newborns, is "a complex disorder meaning that more than one gene as well as environmental factors will be discovered to play a role in its [cause]," study senior author and clubfoot specialist Dr. Matthew Dobbs, an associate professor of orthopedic surgery, said in the news release.

In about 80 percent of clubfoot cases, the cause is unknown, while a familial link plays a role in about 25 percent of cases, according to background information about the study. Males are twice as likely as females to have clubfoot, which occurs more often in the right foot. About half of
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