Gene Region Linked to Mental Ills May Hold Brain Growth Clues

Rare cases of mental retardation were linked to a stretch of DNA that may hold clues to brain development as well as a variety of disorders, scientists said.
Mutations in a gene region called 1q21.1 were associated with 34 cases of retardation, autism, cataracts and facial deformities, said Heather Mefford, an assistant professor of pediatrics at the University of Washington School of Medicine in Seattle, who led a study that will be published tomorrow in the New England Journal of Medicine. Deletions and extra copies of the sequence were both linked to the illnesses, her group said.

Previous studies have tied the same gene region to cases of schizophrenia, the authors said. Further research may shed light on mysterious, incurable illnesses such as mental retardation and autism, Mefford said.

``Clearly, the genes in this region are important for normal brain development,'' she said in a telephone interview.

Each cell in the human body contains a full complement of DNA, a genetic code for making proteins that has about 6 billion individual chemical building blocks called bases. This human genome includes about 25,000 genes, and as many as half may play some role in the brain, said David Ledbetter, a professor of human genetics at Emory University in Atlanta, who wrote a commentary in the same journal.

New techniques of genetic analysis are helping scientists identify additional defects that cause retardation, more than half of which are still unexplained, he said.

`Plenty of Work'

``We still have plenty of work to do but sequencing technologies are evolving pretty rapidly,'' Ledbetter said yesterday in a telephone interview.

More than 40 years ago doctors found they could see large abnormalities under a microscope in DNA of patients with some forms of mental retardation, such as Down's syndrome.

Since then scientists have developed new techniques for finding smaller abnormalities. The latest advance, called comparative genomic hybridization, allows scientists to look for deletions or additions to a patient's genome that don't occur in those of the parents, Mefford said.

The 1q21.1 sequence involves about 1.4 million bases, and may hold eight or nine genes, Mefford said. Children who had the deletion were affected with varying severity of disease, and some parents who had the deletion were completely unaffected, the study said. That suggests that other genes may determine whether the deletion has a severe genetic effect, she said.