Scientists Find Retardation Clues
Emma Ross,
Associated Press Writer

7:26 PM EST; November 12, 1999; London, UK (AP) -- British scientists say they have discovered that a subtle genetic abnormality could be an important cause of unexplained cases of mental retardation in children. Defective genes already are known to be involved in severe learning impairment but, in as many as 70 percent of cases, it is a mystery why children are mentally handicapped. Many cases are assumed to be due to problems that occurred in the womb or in early childhood. But research reported in this week's issue of The Lancet, a British medical journal, found that some children with unexplainable retardation have minuscule abnormalities in the way their DNA is arranged at the ends of their chromosomes.

Such rearrangements, which involves the tail of a chromosome dropping off and attaching to another chromosome, are too small to be detectable with conventional genetic screening methods. The study of 466 children, led by Samantha Knight, a molecular biologist at the Oxford University-linked John Radcliffe Hospital, found that 7.4 percent of moderately or severely retarded children had the abnormality. That would make the defect second only to Down's syndrome as a reason for mental handicap, said John Hamerton of the University of Manitoba, in a Lancet commentary critiquing the work. New technologies that now allow scientists to examine the tiniest submicroscopic segments of the chromosome may eventually provide an explanation for about 20 percent of previously unexplainable cases of moderate to severe retardation, he said. Chromosomes carry genes organized in threads of DNA.

Human beings have 23 pairs of chromosomes in their cells -- one set from the mother, the other from the father. Sometimes the tip of a chromosome, known as a telomere, falls off and reattaches to another chromosome. A person with that condition can remain healthy because, although the genes have rearranged themselves, all the genetic information is there. Problems can occur, however, if a child inherits the abnormal copy of a parent's chromosome that is missing genetic information on the end, but not the chromosome the dropped information attached itself to. Similarly, the child also could have too much genetic information, inheriting the chromosome with the added DNA, but not the one that shed the tail.

Mild mental retardation occurs in about two percent of the population worldwide. More severe disability affects about 5 children out of every 1,000 born. The British scientists looked for the rearrangements in 466 children with unexplained mental retardation and 75 healthy men as a comparison. If an abnormal arrangement was found, the child's parents and other family members were included in the study. The rearrangement occurred in 21, or 7.4 percent, of the 284 moderately or severely handicapped children and one, or 0.5 percent, of the 182 children with mild retardation. None of the 75 healthy men had the abnormality. Among the children with the rearranged DNA, ten had a healthy parent with balanced chromosome changes. In nine of those families, all the other mentally retarded family members tested had the chromosome imbalance, while healthy family members had normal chromosomes or a balanced rearrangement.