Genetic Clue to FAS

Researchers turn up genetic clue to curse of fetal alcohol syndrome
Thursday, 10 July 1997
St. Louis Post-Dispatch

Researchers have found an important clue about how alcohol consumed by a pregnant woman damages a developing fetus.

In tests on laboratory mice, the scientists found that alcohol blocks the work of a gene key to development of a normal brain, heart, skull and other parts of the body.

The discovery is important to understanding the impact of fetal alcohol syndrome, one of the major preventable causes of birth defects and childhood disabilities. The syndrome, which affects about 12,000 babies a year, can result in mental retardation, learning disorders, facial abnormalities and stunted growth.

The findings were reported in the current issue of the Proceedings of the National Academy of Sciences.

The way alcohol inflicts damage has long been a mystery. Many researchers believe alcohol stages a multi-front assault on many parts of the body. The new research, at Washington University in St. Louis, suggests a simpler attack.

``We have come across a big clue,'' said Leonard Rifas, one of the scientists. He conducted the research with Dr. Dwight Towler and Dr. Louis Avioli. All are with the university's medical school.

The scientists found that alcohol early in fetal development interferes with the process by which the body switches on the gene, called MSX2.

The researchers cautioned about applying the discovery to humans. But they pointed out that the gene performs the same function in mice, humans and other mammals.

``This is an intriguing step,'' said Dr. Stephen Braddock of the University of Missouri at Columbia, a specialist in fetal alcohol syndrome. Braddock emphasized that he had not yet seen the study.

``It's likely that many genes are involved,'' he said, noting that alcohol can affect the developing brain throughout pregnancy.

Each human cell has about 100,000 genes, all strung together in the genetic material known as DNA. They form a blueprint that directs construction of the body. Various genes become active at different times and in different cells.

The researchers focused on a gene believed important in the development of bone, brain, heart and other tissue in the first trimester of pregnancy.

``The timing seems to be critical,'' Rifas said in an interview.

The researchers focused on the MSX2 gene because a natural mutation of this gene causes physical defects similar to those in fetal alcohol syndrome.

They injected pregnant mice with alcohol early in gestation, and then watched for building-block chemicals normally produced in the embryo when the MSX2 gene is functioning properly. These chemicals were absent in the alcohol-exposed embryos. And these embryos were half the size of normal mice embryos when removed midway through the pregnancy.

The scientists believe that alcohol somehow inhibits a complex pathway of chemical signals that tell the gene when to switch on during normal development.

``We have quite a bit of work to do before we can pinpoint the mechanism,'' Rifas said. ``But we clearly have a new avenue through which to investigate the toxic effects of alcohol leading to fetal alcohol syndrome.''

The National Organization on "" Fetal Alcohol Syndrome has a Web site.

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