A team of scientists, led by the director of UC Davis M.I.N.D. Institute, has discovered that some men who carry the gene for fragile X syndrome develop tremors, memory problems and other debilitating neurological problems later in life. Fragile X is the most common inherited cause of mental retardation. The results of the research are being published in this month's issue of Neurology.

"We have known that men and women who carry a mutation of the fragile X gene are more likely to have problems with anxiety, attention deficit and hyperactivity disorder or premature menopause," said Randi Hagerman, UC Davis M.I.N.D. Institute director and an internationally recognized expert on fragile X syndrome. "But this is the first time we have found a group of men in their 50s and 60s who suffer from this unique tremor problem and whose grandchildren suffer from fragile X syndrome, which includes autism."

Richard Darwin, a retired electrical construction foreman, is one of Hagerman's patients and suffers from hand tremors and some mobility problems.

"When Richard first started experiencing tremors in his hands, we thought maybe it was a work-related injury from repetitive motions," said Darwin's wife, Marilyn. "It wasn't until our daughter found out that our grandson had fragile X syndrome that we discovered there was a connection."

Darwin, now 64 years old, retired when he was 58 because of his tremors.

"He had to retire early because he was having trouble using his tools. It became too dangerous for him to continue working with electricity," Mrs. Darwin said.

Paul Hagerman, UC Davis School of Medicine professor, molecular biologist, and physician, is involved in genomic research on autism. He first made the connection in his research of children with autism and fragile X, when he discovered elevated levels of messenger RNA in several children. Messenger RNA carries the duplicated DNA code to the cytoplasm of the cell where protein is made. Discussion of family histories led the research team to the grandparents.

To date, the team has identified 10 older men with similar progressive nervous system degeneration, Randi Hagerman said. These problems include tremors in the hands leading to illegible writing and inability to hold drinking glasses, unsteady gait that can cause patients to lose balance, extreme slowness in movement, and facial characteristics similar to those who suffer from Parkinson's disease.

Each of the men observed first noticed tremors in one hand when in his 50s or 60s. Their problems have progressed over a number of years to the point that the men are severely limited in performing normal daily activities, she said. All of the men have at least one grandchild with fragile X syndrome.

"Although we have discovered a set of problems in these men that appears to be a previously unidentified syndrome, we still need more research," she said. "We have no idea at this point how prevalent this disorder is among grandfathers of fragile X children."

The M.I.N.D. (Medical Investigation of Neurodevelopment Disorders) Institute was founded in 1998 as a unique interdisciplinary organization of parents, community leaders, researchers, clinicians and volunteers. Institute investigators study and treat neurodevelopmental disorders such as autism, fragile X, dyslexia, attention deficit disorder and Asperger's syndrome. Randi Hagerman, a pediatrician, joined the institute in December as its director. Her husband, Paul, joined UC Davis in the Department of Biological Chemistry and as an associate researcher with the M.I.N.D. Institute.

"From a research standpoint, this discovery helps scientists at the M.I.N.D. Institute to pinpoint areas to investigate in their primary quest to identify biomarkers or early-warning signs, of autism, fragile X and other neurodevelopmental disorders," she said. "I am excited that our researchers have an opportunity to better understand, from a molecular view, how the problems of the grandfathers relate to the problems of the children who have fragile X."

For the Darwins, helping researchers unravel the connection in order to aid other families is a bittersweet reward.

"Richard had plans for his retirement, but is not able to do most of the things he wanted to do," Mrs. Darwin said. "But we both are happy that he can contribute to the gene research that is going on so that other families can know if they are carriers, and hopefully so that there can be a way to fix the problem."

The team that identified this syndrome include researchers from the UC Davis M.I.N.D. Institute and the Department of Biological Chemistry at the UC Davis School of Medicine, the Departments of Neurology and Medicine at the University of Colorado Health Sciences Center, the Fragile X Treatment and Research Center at The Children's Hospital, Denver, and Kaiser Permanente in Stockton.

For more information about the UC Davis M.I.N.D. Institute, visit the web site http://www.mindinstitute.org