Science Begins to Solve Mystery of Speech

Convinced that genes had everything to do with a severe speech and language disorder affecting three generations of a British family, scientists at the University of Oxford scanned their chromosomes and found the culprit: a single genetic defect on chromosome 7.

Anthony P. Monaco and his colleagues are the first to link a gene to the unique human trait of speech. While it may hold keys to some very important questions about the nature of language and speech, odds are it won’t help correct the deficits in this family--at least not in current generations.

“This is an exciting study,” said Dennis Drayna, an expert in genetics at the National Institutes of Health in Bethesda, Md. “This is ultimate proof: a strong effect of a specific gene.”

Once researchers find the exact gene in question and figure out the substance it produces, they may better understand what it is actually doing to cause these speech and grammar problems. Eventually, it may be possible to unravel the many complexities that come together in allowing humans to speak, Drayna said.

The work, published in January’s Nature Genetics, was a collaboration by Oxford scientists and colleagues at the Institute of Child Health in London, to which half of a 30-member family was referred a decade ago. Institute scientists conducted neuropsychiatric exams on the affected family members, all of whom cannot speak coherently and who make repeated grammatical errors. They have no other pervasive thought or motor problems. Their intelligence is normal.

Scientists also found that each affected family member--from a grandmother to her children and her children’s children--has an underdeveloped caudate nucleus. This region of the brain acts like a relay station, shuttling information between areas in the motor cortex to projections in the frontal lobe involved with speech and language.

This would explain, says Faraneh Vargha-Khadem, a neuro-psychologist at the child institute and a co-investigator, their core deficit: an inability to coordinate small oral motor movements. Words and sentences never seem to come out right.

This primary deficit has affected the family members’ ability to learn language, follow rules of grammar and semantics and express themselves. The result has been generations of learning disabilities in reading and writing.

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Dozens of single genes can cause mental retardation, but the brain effect is more widespread. This defect on the long arm of chromosome 7 seems to be very specific for the motor movement that involves speech and for the ensuing language problems.

K.E., 46, who shares the speech and language problem with four of her nine children, was at the child-health institute with family members celebrating the news.

“We are very happy,” she said in a very quick but measured tone. “Technology of today--they’ve come up with results. They say it is a single gene. We are quite pleased . . . We are hoping it helps the next generation of our family.” She said other members of her family have much more severe speech and language problems than she does. “I take my time. It is much harder.”

K.E.’s mother also is affected, as are her two sisters, one brother and their children.

The yet-unknown gene is called, appropriately, Speech I. The scientists knew they were dealing with a genetic trait that seemed to require only one gene to cause the problem.

Drayna said the British scientists’ finding suggests it may one day be possible to “pick apart these complex functions, like language, one gene at a time.”

Monaco said his lab was contacted by Marcus Pembrey of the child institute and asked to collect DNA from K.E. and her family members and scan the chromosomes for any genetic mutations. They had 300 markers in all that they were going to test.

A month into the project, Simon Fisher struck gold on the 50th marker. “He came bursting into me,” Monaco recalled. They called their collaborators right away.

Monaco said there are three candidate genes on chromosome 7 that the researchers are analyzing, but it really could be any one of a hundred in that region. At present, these genes have been individually placed into hamster cells to see whether any cause the same mutation. “If not, we have to go through gene by gene,” Monaco said.

“You never know what you are going to get until you get there.”

Ultimately, Monaco and other scientists want to understand the genetic involvement in other language deficits such as autism and dyslexia and even attention deficit disorder.

Recently, the geneticist collected DNA from 100 families with more than one member suffering from autism. Interestingly, it seems that many of those with autism also seemed to have a genetic mutation on the same area on the seventh chromosome.