Study reported in Nature Genetics identified link in nine of 10 people with the same deletion in chromosome 15.

The loss of a gene through deletion of genetic material on chromosome 15 is associated with significant abnormalities in learning and behavior, according to a consortium of researchers led by Baylor College of Medicine (BCM). “This gene encodes a subunit of a nicotinic receptor,” explains Arthur L. Beaudet, M.D., chair of molecular and human genetics at BCM.

“It is a gene that mediates the response to nicotine via a receptor whose normal ligand is acetylcholine.” The gene encodes an ion channel, and defects in ion channels have previously been associated with forms of epilepsy.

The study appears online in Nature Genetics and is titled “A small recurrent deletion within 15q13.3 is associated with a range of neurodevelopmental phenotypes.”

Previously, a larger deletion containing more genes had been reported in people with the same constellation of disorders. In this work, the BCM-led team found that a smaller deletion of genetic material, the whole gene called CHRNA7, and a part of another was associated with similar problems in 10 members of four families.

“This research goes about 95 percent of the way to pinning these problems in a specific group of individuals to this gene,” says Dr. Beaudet. He believes that the deletion will be identified in more people with behavioral problems as well as schizophrenia, developmental delay, and epilepsy. The gene’s role in schizophrenia has been under study for some time.

In this study, an international group of researchers identified 10 people from four unrelated families with the same deletion in the chromosome. Of the 10 subjects, nine had developmental delay and/or mental retardation. Four had seizure disorders or an abnormal electroencephalogram.

In two of the families studied, the patients had inherited the deletion from a parent. In one family, researchers found the same deletion in the patient’s mother, two siblings, maternal aunt, and maternal grandmother. Both the patient’s mother and aunt had mental retardation and epilepsy, while both siblings had developmental delay. The patient had severe mental retardation and obesity and mild facial dysmorphism.

A second patient with impaired growth and severe developmental delay inherited her deletion from her mother, who had normal intelligence but had suffered from epilepsy from childhood.

“If insufficient expression of the nicotinic receptor causes most or all of the problems associated with deletions in this particular area of chromosome 15, then it offers a target for drug treatment,” points out Pawel Stankiewicz, M.D., Ph.D., assistant professor of molecular and human genetics at BCM.

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