DNA furnishes tips to mental retardation.

Rearrangements at the ends of chromosomes, so subtle that they have eluded conventional genetic screening techniques, represent one of the most common causes of moderate to severe mental retardation, a new study finds.

The discovery raises prospects for better understanding some of the 40 percent of such cases in which no cause can be determined, contends a team led by geneticist Samantha J.L. Knight of John Radcliffe Hospital in Oxford, England.

"We suggest that subtle chromosomal rearrangements are the second most common cause of moderate to severe mental retardation after Down's syndrome," the team concludes in the Nov. 13 LANCET.

The newly identified DNA rearrangements often run in families, underscoring the need for genetic screening of children who have mental handicaps of unknown origin, the researchers hold.

Knight and her colleagues developed a laboratory technique for finding rearrangements of unusually short stretches of DNA, which usually elude standard probes. A pilot study employing the new method suggested that changes on chromosome tips often occur in children with unexplained mental retardation.

The researchers then examined chromosome ends in 284 children with moderate to severe, unexplained mental retardation. All the youngsters had IQ scores lower than 50, though their parents had normal IQs. The team also conducted genetic analyses of 182 children with unexplained mild mental retardation (IQ scores between 50 and 70) and 75 men with IQ scores in the normal range (between 90 and 110).

Subtle chromosome rearrangements had occurred in 21 children with a moderate to severe mental handicap, a frequency of 7.4 percent. Only one mildly retarded child, for a frequency of 0.5 percent, and none of the controls displayed these DNA alterations.

Further testing established that for 10 of the 22 mentally retarded kids with chromosomal rearrangements, the mother or father exhibited a pattern of chemical reshuffling along a chromosome end. It differs from the child's abnormality. These parents may possess DNA characteristics that translate into mental retardation for some of their offspring, the scientists propose.

Moreover, in 9 of the 10 families, siblings and other relatives with mental retardation also displayed signature alterations along chromosome tips.

Genetic testing with the new technique will improve counseling for retarded people harboring subtle chromosome changes and their families, comment geneticists John L. Hamerton and Leonie Stranc of the University of Manitoba in Winnipeg in the same journal.