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Dyslexia's DNA Clue: Gene takes stage in learning disorder

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8:49am, August 27, 2003
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For the first time, scientists have identified a gene that appears to influence the development of at least some cases of dyslexia.

This learning disorder is characterized by difficulties in perceiving sounds within words, spelling and reading problems, and troubles with written and oral expression. It's estimated that dyslexia affects at least 1 in 25 people. Although scientists are investigating dyslexia's suspected neural roots (SN: 5/24/03, p. 324: Scripted Brains: Learning to read evokes hemispheric trade-off), the condition's causes remain unknown.

If confirmed in further studies, the new genetic finding represents a major step forward for dyslexia researchers. Until now, investigators have only been able to link dyslexia to alterations along stretches of DNA containing tens or hundreds of genes. The most prominent of these genetic segments are located on chromosomes 6 and 15.

A team led by geneticist Juha Kere of the Karolinska Institute in Huddinge, Sweden, narrowed the search to a gene called DYXC1 on chromosome 15. Two disruptions of this gene substantially raise the odds of developing dyslexia, the scientists report in an upcoming Proceedings of the National Academy of Sciences.

"Certainly, there are other genes involved in dyslexia," Kere says. Even so, he adds, "our research may [eventually] help doctors to diagnose dyslexia more accurately."

He and his colleagues first determined that a break had occurred at a specific location on the DYXC1 gene in the three dyslexic members of a Finnish family-the father and two daughters-as well as in a son without the condition. Molecular analyses indicated that the genetic break prevented the production of the protein encoded by the DYXC1 gene.

The researchers then probed the same gene in 109 children and adults diagnosed with dyslexia and in 195 others who had no learning disorder. The previously observed DYXC1 break appeared in nearly 9 percent of those with dyslexia, compared with fewer than 3 percent of the comparison group.

Another DYXC1 disruption, which yields an altered version of the gene's protein, occurred in about 12 percent of the dyslexic group, compared with roughly 5 percent of the others.

Evidence of the gene's activity appears in the brain, the scientists say. Their analyses of preserved human brains indicate that only certain brain cells respond to the DYXC1 protein. The neural function of the protein remains unknown, Kere says.

The DYXC1 protein's molecular makeup in people differs to a surprising extent from that of corresponding proteins in chimpanzees and other apes, Kere notes. "This gene may reveal important evolutionary differences in how our brains and those of other primates work," he says.

Geneticist Shelley D. Smith of the University of Nebraska Medical Center in Omaha calls the new report "a really neat finding." The challenge is to confirm the results in larger samples of people with dyslexia and then determine how the gene and its protein work, Smith says.

Her team is looking for genetic alterations on chromosome 6 that influence dyslexia.

Further work needs to establish whether the DYXC1 gene influences other developmental disorders, such as speech problems and attention-deficit hyperactivity disorder, adds psychologist and geneticist Elena L. Grigorenko of Yale University, in a comment slated to appear with the new report. Still, Grigorenko dubs Kere's study "an exciting beginning of a new stage of research into genetic pathways of dyslexia."

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