Researchers at the UC Davis M.I.N.D. Institute will launch the first widespread newborn screening for the genetic mutation that results in fragile X syndrome, the single most common inherited cause of mental retardation.

Using a test they developed, the researchers will screen as many as 30,000 infants during the next five years as part of a $2.3 million pilot study that lays the groundwork for universal newborn screening of all infants in the United States for the fragile X mutation.

"This is a very important advance for the understanding and treatment of fragile X syndrome and paves the way for early identification and early intervention for these children," said M.I.N.D. Institute medical director and study senior investigator Randi Hagerman.

The study will for the first time allow families of infants with fragile X to learn shortly after birth whether their child will have the disorder, which is associated with physical anomalies, intellectual deficits, learning disabilities and behavioral and psychiatric problems.

"Identification of the condition in early infancy will allow families to seek crucial early intervention services for their children that we hope will mitigate the disabling affects of the disorder," said lead study investigator Flora Tassone, associate research biochemist in the department of biochemistry and molecular medicine.

Though fragile X syndrome is rare - occurring in approximately 1 in 3,600 males and 1 in 4,000 females - researchers believe widespread genetic testing will reveal that a much higher incidence of the condition exists than is currently believed.

Fragile X syndrome is also the most common known genetic cause of autism, which affects 1 in 150 children in the United States. Approximately one-third of all children with fragile X syndrome have autistic-like symptoms. Of children diagnosed with an autism spectrum disorder, approximately 5 percent have fragile X syndrome.

The blood spot study will allow researchers to offer screening for fragile X to the parents of all newborns at UC Davis Medical Center in Sacramento, Calif., and to all parents of infants born at Rush University Medical Center in Chicago. Study participants in Chicago will be followed by co-principal investigator Liz Berry-Kravis.

The significance of widespread newborn screening is amplified by the fact that adults related to children with fragile X syndrome often suffer from associated but frequently misdiagnosed ailments.

One such ailment, first identified by a team led by Hagerman, is fragile X-associated tremor/ataxia syndrome or FXTAS (pronounced fax-tass), a condition affecting older males and some older females that is routinely mistaken for Parkinson's disease or other movement disorders.

Males tend to be more severely affected by fragile X than females because women have two X chromosomes. If one of a woman's chromosomes has the fragile X mutation, the second X chromosome can compensate.

Hagerman, one of the world's leading experts on fragile X and related conditions, said that, while the newborn screening study is not specifically designed to offer treatment, the diagnosis will open the door to new therapies for both infants and adult family members who are subsequently diagnosed with related conditions.

"Once we have identified the affected infants, we will propose treatment options for them and also will assess the gene's impact on other family members. In many instances, families may not even know that the gene exists," Hagerman said.

"This will allow us to also look at a larger group of extended family members and the effects that the mutation may cause," she said. "That includes emotional problems, aging disorders, FXTAS and premature ovarian failure - all of that."

In addition, genetic counseling for parents of children identified as having fragile X syndrome will be crucial, said Hagerman, because such families are at an increased risk of having additional children with the condition.

The blood spot test was developed by Tassone and Paul Hagerman, professor of biochemistry and molecular medicine. They worked on optimization of the methodology for the test for the past two years.

Fragile X syndrome and its associated disorders are the result of a mistake in the number of repeats of three nucleotides on the FMR1 gene on the X chromosome. A normal X chromosome generally has between five and 55 repeats of these nucleotides. Repeats above 200 result in fragile X syndrome. Individuals with between 55 and 200 repeats, called carriers, are susceptible to a wide range of ailments, like FXTAS and premature ovarian failure.

The test uses small drops of blood drawn from infants shortly after birth to test for the fragile X mutation. It employs a polymerase chain reaction (PCR) technique that amplifies the expression of the FMR1 gene, allowing researchers to detect the number of nucleotide repeats, from the normal number of repeats to the full fragile X mutation of 200 repeats or more.

Existing tests for fragile X have had a variety of limitations, Tassone said, including not being able to detect the full range of genetic mutation in both males and females.

"For effective newborn screening, a test has to be quick, cheap, it has to work on a very small amount of DNA and it has to detect everyone," Tassone said. "This test responds to all of those requirements."

The blood spot study is part of a larger, five-year grant from the National Institutes of Health to the Fragile X Research Center of the University of Washington Center for Human Development and Disability.

In addition to the M.I.N.D. Institute, the grant is funding studies at several other institutions, including the University of Washington, the Fred Hutchinson Cancer Research Center in Seattle and the University of Illinois at Champagne-Urbana, that will examine various aspects of the fragile X gene's function, including how its stem cells develop.

The UC Davis M.I.N.D. Institute, in Sacramento, Calif., was founded in 1998 as a unique interdisciplinary research center where parents, community leaders, researchers, clinicians and volunteers collaborate on studies of autism and other neurodevelopmental disorders. More information about the institute is available on the Web here.

UC Davis M.I.N.D. Institute