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New insight into most common forebrain malformation
Date:8/11/2008

St. Jude Children's Research Hospital scientists have identified one of the molecular mechanisms underlying the genetic brain malformation called holoprosencephaly (HPE). The findings not only yield insights into the most common developmental malformation of the anterior brain and face in newborns, but also help in understanding the intricate process by which the brain forms in the developing fetus.

Led by St. Jude geneticist Guillermo Oliver, Ph.D., the researchers published their findings in the August 11, 2008, issue of the journal Developmental Cell.

"These findings are important, because, while genes that cause HPE have been identified, the interactions among those that produce HPE are not only complex, but poorly understood," Oliver said. "This represents a first step in understanding the mechanism of that interaction."

HPE occurs in about one in every 250 fetuses, frequently causing miscarriage or stillbirth. HPE is present in varying degrees in one in every 16,000 newborns. The disorder is characterized by a failure of the developing brain to separate into right and left hemispheres. Besides brain abnormalities, HPE is characterized by facial malformations such as cleft lip and cleft palate. HPE has been traced to mutations in any of nine genes, although researchers believe the disorder is also influenced by environmental factors such as maternal diabetes, infections during pregnancy or drugs.

In their studies, the researchers sought to understand the role in HPE of a gene that codes for a protein called Six3. In previous studies, Oliver and his colleagues had identified the Six3 protein as critical to fetal brain formation. Also, other studies had implicated defect-causing mutations in Six3 as involved in causing HPE, but they did not know the molecular mechanism by which Six3 promotes HPE.

One clue to Six-3's role in HPE arose from the fact that most of the other HPE-causing genes produce malfunctio
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Contact: Carrie Strehlau
media@stjude.org
901-595-2295
St. Jude Children's Research Hospital
Source:Eurekalert

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