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Newly identified gene linked to brain development

BOSTON -- With the identification of the gene responsible for a newly recognized type of mental retardation, researchers at Beth Israel Deaconess Medical Center (BIDMC) have also discovered what appears to be the key target in the evolution of the frontal lobes of the brain's cerebral cortex. The findings, reported in the March 26, 2004, issue of the journal Science, offer a key insight into the complex puzzle of human brain development and the evolution of human behavior.

"The cerebral cortex is the part of the brain that distinguishes humans from other species," explains the study's senior author Christopher A. Walsh, MD, PhD, a Howard Hughes Medical Institute investigator in the Neurogenetics Division at BIDMC and Bullard Professor of Neurology at Harvard Medical School. "And the frontal lobes are the part of the cortex that govern social function, cognition, language, and problem-solving. Patients with damage to the frontal lobes exhibit changes in behavior, and frontal lobotomies were once performed to alter aggressive behavior."

Bilateral frontoparietal polymicrogyria (BFPP), a recessive genetic disorder characterized by mental retardation, gait difficulty, language impairment and seizures, results in severely abnormal architecture of the brain's frontal lobes, as well as milder involvement of parietal and posterior parts of the cerebral cortex.

In this new study, lead author Xianhua Piao MD, PhD, and colleagues used magnetic resonance imaging (MRI) to identify BFPP patients, and then used linkage analysis, homozygosity mapping, and candidate gene analysis to identify the BFPP gene as GPR56, located on an area of chromosome 16.

"We showed that mutations in GPR56, which encodes an orphan G protein-coupled receptor [GPCR], were responsible for BFPP," explains Piao. GPR56 is expressed in the neural stem cells produced in the cerebral cortex, and plays an especially important role in the frontal portions of the cortex.

Walsh's labo
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Contact: Bonnie Prescott
bprescot@bidmc.harvard.edu
617-667-7306
Beth Israel Deaconess Medical Center
25-Mar-2004


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