What do the following famous figures have in common? ThomasEdison, John D. Rockefeller, Auguste Rodin, Michelangelo andCher?If you answered that all of the above suffered from dyslexia, youare right.People tend to think of dyslexia as a childhood inability to writeletters and words in their right order. Actually, there's a lot more tothe disorder than that. For one thing, although it shows up in ayoungster when he or she starts school, dyslexia is a lifelonginability to sort out the three R's _ reading, writing and `rithmetic_ especially, spelling.Contrary to widely held opinion, said statistical geneticist LonCardon, kids do not necessarily "outgrow" dyslexia as they mature."It's an interesting question," Cardon told BioWorld Today."Rather, they develop very elaborate compensatory mechanisms todeal with it. So they still may suffer from difficulties with reading,and find ways around it."He noted that sometimes adults with dyslexia are discriminatedagainst in the workplace, fired because they don't read and spellwell.Cardon directs statistical genetics at Sequana Therapeutics, Inc., inLa Jolla, Calif. Another false impression, he observed, is thatamong dyslexic children, there are more boys than girls. Back in1950, a Swedish geneticist named Bertil Halgren studied twins andtheir family histories of the disorder. He concluded that dyslexia isan inherited, sex-linked dominant trait. Subsequent reports to thisday claim that males heavily outnumber females.If these findings are correct, Cardon points out, then one must lookfor the dyslexia gene on the X chromosome. To the contrary, asreported in Science out today, he has found its fingerprints onchromosome 6.Gender predominance in dyslexia, Cardon said, "is somewhat of acontentious issue, because it may just be that males are more easilyacquired for genetic study." He added that the dyslexia sometimesdiagnosed by school teachers often reflects "quite differentclassroom problems, such as attention deficit or behavioralproblems."Cardon's paper in today's Science is titled, "Quantitative trait locusfor reading disability on chromosome 6." This discovery, he said,"represents the first time that evidence for a major gene associatedwith a complex behavioral trait has been found in independentpatient populations."Dyslexic Kids Have Normal IQsOne of the two populations he studied consisted of 358 individualsfrom 19 families with a three-generation history of specific readingdisability. The other group comprised 50 pairs of fraternal twins, inwhich at least one twin had had reading problems at school.Cardon emphasizes that dyslexic children, despite their frequentnegative self-image and the prejudices of teachers, peers andparents, are not stupid or dumb. "We selected children with normalIQs, yet indicated by their teachers as being reading-disabled. Wegave them a well-defined battery of psychometric tests, for wordrecognition, spelling and comprehension."The test scores enabled the dyslexia gene-hunters to discriminatetrue reading disability from mere abnormally delayed readinglevels. To scrutinize the genomes of their case samples on suspectchromosomes, the team adopted a statistical method of linkageanalysis called interval mapping. "Instead of taking one DNAfragment at a time," Cardon explained, "and looking around it tosee if there is a gene to the left or the right, we took pairs.Systematically walking down the chromosomes, we looked betweenthe pairs of DNA markers _ polymorphisms _ looking forsimilarities corresponding to those in the disorder."Hot Spot On Number SixThe team searched chromosomes 1, 12 and 15 before fixing on theshort arm of chromosome 6, "the only location that showedsignificantly similar results on both samples." It confirmed thatdyslexia has an autosomal dominant inheritance pattern.This stretch of chromosome 6 turned up an unexpected correlation:"That particular region," Cardon said, "harbors the well-knownhuman leukocyte antigen complex of genes for autoimmunedisorders. And, he continued, "there's a long-standing observationof increased prevalence of some autoimmune disorders in somedyslexics over the normal population. These autoimmune entitiesinclude thyroid, migraine, asthma and hay fever."A co-author of today's Science paper is medical geneticist ShelleySmith, who directs the Center for Hereditary CommunicationDisorders at Boys Town National Research Hospital in Omaha.Next week in Montreal, she will present a poster summarizing theScience findings at the 1994 annual meeting of the AmericanSociety of Human Genetics.How does Sequana plan to commercialize this line of research? "Atthe moment," Cardon said, "all we have is a chromosomal region.We don't actually have the gene for dyslexia, or the mutations forit."When we take the next step," he added, "go in and clone it, andwork toward a diagnostic, that will present more opportunities." Heforesees mass screening to single out true dyslexic children, "thentargeting them for appropriate remediation."Dyslexia therapy will be educational, not pharmaceutical. "Manyspecial learning classes for reading are already in place in schools,"he pointed out. "The earlier we can target these children for speciallearning, special education, behavioral tutoring _ the assumption is_ the better off they will be, the better able to deal with theirdeficit."Clinical neuropsychologist Bruce Pennington sees a lot of dyslexiapatients in his learning disabilities clinic at the University ofDenver. "Dyslexia," he told BioWorld Today, "is probably the mostcommon learning disability there is, with incidence in thepopulation ranging from three to 10 percent."Pennington, a co-author of the Science paper, hopes that "thepaper's impact would be clear recognition that this is a real medicalcondition with a real biological basis." He marvels that "There arestill people who question whether dyslexia exists," and added, "So Ihope it helps to settle that question once and for all." n
-- David N. Leff Science Editor
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