NOTE TO READER: The following article is a newspaper report from the Salt Lake City Tribune, and like most newspaper articles, may have a number of factual errors. Nonetheless, it is an interesting report of one of the latest discoveries about the nature of Williams syndrome and should interest you.

UTAH SCIENTISTS LINK GENES TO ABILITY TO THINK STRAIGHT

by Lee Siegel

July 12, 1996

Utah scientists found evidence that a genetic defect makes it difficult for some people to assemble furniture, follow maps or do other tasks that require thinking in three dimensions. "To our knowledge, it's the first time somebody has shown that a mutation of a specific gene causes impairment in the development of a specific thought process,'' said Mark Keating, who led the study at the University of Utah's Howard Hughes Medical Institute.

The findings were published today in the journal Cell by Keating, six Utah colleagues and researchers from the University of Nevada at Las Vegas, Emory University in Atlanta, Indiana University, the National Institutes of Health and the Institute of Neurology in London. Keating predicted the study would generate controversy because "the big issue is whether you can tie a gene to something as complicated as thought processes."

There's a debate among neuroscientists as to whether you can break down our brain and our thought processes into simple elements like genes and proteins. This study shows you can.'' One scientist who reviewed the study anonymously at the journal's One scientist who reviewed the study anonymously at the journal's request initially wrote that the link between the mutation and impaired 3-D thinking was ``extremely weak.''

Another anonymous reviewer agreed, but added: ``Nevertheless, the paper is of great importance and is highly provocative. This is certainly exciting and ground-breaking research.'' Because of those reviews, Keating rewrote his study to make his case more strongly, and Cell published it.

Abram Hostetter, a Hershey, Pa., psychiatrist and spokesman for the American Psychiatric Association, said Thursday that Keating's study is important and may not be controversial because it fits the current trend of seeking genetic underpinnings for human cognitive abilities and mental of seeking genetic underpinnings for human cognitive abilities and mental illness. Keating's study ``demonstrates that a person's concept formation is determined by the chemistry of the brain and, if there is a [genetic] defect, that person may not be able to think as clearly,'' Hostetter said. He added the discovery raises the prospect of devising treatments to reverse the impaired 3-D thinking ability.

The study involved people with Williams syndrome, which occurs in one of every 20,000 newborns and is characterized by several abilities and disabilities. Williams syndrome patients suffer heart disease, particularly narrowing and clogging of the aorta or other major arteries. Other typical symptoms and clogging of the aorta or other major arteries. Other typical symptoms can include mental retardation, excellent musical abilities, high calcium levels in the blood, impaired 3-D thinking ability, a rich vocabulary, elfin facial features, and extreme sociability known as a "cocktail-party personality.''

Keating's team previously showed the heart defects are due to a mutation that leaves Williams syndrome patients missing one copy of a gene named elastin, which is believed to make arteries flexible and more resistant to clogging. He also showed previously that Williams syndrome patients lack a section of DNA adjacent to the elastin gene. That DNA was believed to carry other genes that, when absent, result in other symptoms of the syndrome.

In the new study, Keating and colleagues analyzed two Williams syndrome families in which 25 people had heart disease and impaired 3-D thinking, but none of the other typical symptoms. The impairment in 3-D thinking ability means such people have difficulty following a simple bus route on a map, drawing simple objects, setting a table and assembling models, puzzles or furniture. The missing DNA in the two families was shorter than the missing DNA in typical Williams syndrome patients. Keating and colleagues showed the shorter stretch of DNA contains only two genes: elastin and a gene named LIM-kinase1.

From that, they deduced the absence of LIM-kinase1 must be the mutation responsible for impaired 3-D thinking ability in affected members of the two families. One family is from Utah, Nevada and Georgia. The other lives in Louisiana. Keating suspects at least one other gene is missing in people with other typical Williams syndrome symptoms, and that gene causes the symptoms other than heart disease and impaired 3-D thinking ability. Genetic defects previously have been implicated in Alzheimer's disease. But except for LIM-kinase1, no other mutation has been tied to defective development of a thought process, in contrast to Alzheimer's degeneration of already developed abilities in older people, Keating said. Researchers previously knew the LIM-kinase1 gene produces a protein that is found in the brain. Williams syndrome patients are missing one of two LIM-kinase1 genes, which means they make half as much of the protein. Keating speculated that one of the protein's normal roles is to aid development of nerve cells responsible for 3-D thinking ability, so lacking enough of the protein impairs that ability. Keating called his study "one of the first molecular toeholds we have into understanding human cognition -- how our brains work and how our brains develop.'' University of Utah researchers who helped Keating conduct the study are graduate students J. Michael Frangiskakis and Amanda Ewart, postdoctoral fellow Christoph Proschel, neuoscientist Mark Noble, technician Donald Atkinson and molecular geneticist Shannon Odelberg.