Clemson researchers identify mental retardation gene

Clemson University and Greenwood Genetic Center researchers have found a link between a single gene and mental retardation. Dr. Anand K. Srivastava and his colleagues report their findings in the June 28 edition of the internationally respected journal, Science.

The researchers found a single gene, Angiotensin II receptor 2 — known as AGTR2 — on the X chromosome that may trigger mental retardation when the gene is abnormal. Srivastava, associate research geneticist in Greenwood and adjunct research professor at Clemson, has linked this gene to mental retardation in males.

"The identification of a single gene mutation that may prove to be the cause of some cases of mental retardation is very encouraging," said Duane Alexander, M.D., director of the National Institute of Child Health and Human Development, which funded the study. "This advance not only may lead to insights into a variety of new therapies, but may also help us to better understand the processes involved in normal brain development."

The research was conducted at the Center for Molecular Studies at the J.C. Self Research Institute of Human Genetics in Greenwood. "Identification of genes that cause mental retardation and other human disabilities is a major focus of the institute," said Dr. Charles Schwartz, head of the research program.

A single patient led scientists to research the connection. Knowing beforehand that the mentally retarded female patient had an abnormally arranged X chromosome, they theorized that a single gene was silenced by the rearrangement, resulting in the patient's developmental disabilities.

Dr. Srivastava's team identified the gene that was silenced and then studied it in 590 male patients with unexplained mental retardation, identifying mutations in eight of them.

"Although an AGTR2 mutation appeared to be present in only 1.5 percent of males with unexplained mental retardation, this percentage is significant," said James Hanson, M.D., chief of NICHD's mental retardation and developmental disabilities branch.

"With 30,000 to 35,000 total genes in the human body, the discovery of even a single gene that may play a pivotal role in brain development could be an extremely important discovery. This study also shows that the technique of identifying candidate genes in a single individual with mental retardation and testing them for mutations is useful for identifying genes related to mental retardation."

Chromosomes are thread-like chains of genes, which carry genetic information for specifying proteins to build the cells that create a body. An X chromosome regulates female genetic traits; a Y chromosome expresses male characteristics.

Women have two X chromosomes, and men have an X and Y chromosome. The genes on a chromosome act like instruction manuals, directing the body to make proteins that build cells, which become organs and other body parts. When a gene is broken, it fails to make the correct protein, which can cause disease or disabilities.

"Genetics experts believe that more than 100 of the approximately 1,200 genes on the X chromosome are involved in brain development and function," said Schwartz.

The precise function of the AGTR2 gene has not been determined. It is not known, for example, whether the gene interrupts early formation of the brain or disturbs the later function of the brain.

The X chromosome AGTR2 gene is similar to the AGTR1 gene, which plays a part in blood vessel development, blood pressure regulation, water and electrolyte balance and hormone secretion. The researchers suspect that AGTR2 is linked to blood vessel function or development, likely to be important for brain formation or function.