Fragile X repeats clog protein synthesis.

In fragile X syndrome, as well as several other disorders with genetic components, problems arise because of mutations in the affected cells' genetic codes (SN: 7/10/93, p.20). For some reason, sections of particular genes contain multiple sets of three nucleotides. Typically, 50 sets of these threesomes exist, one right after another. But in aberrant cells, the number of these so-called trinucleotide repeats can exceed 250.

Most of the time, this excessive stretch of DNA repeats never gets transcribed into messenger RNA, and subsequently translated into a protein. But in at least one man with a mild case of fragile X syndrome, the transcription machinery of some cells waded through the gene's threesomes and sometimes even made protein, says Yue Feng of Emory University School of Medicine in Atlanta.

Feng and her colleagues removed samples of cells from this man and grew them in the laboratory. In these, the affected fmr-1 gene had 57, 168, 182, 207, 266, or 285 repeats. The degree to which these genes were abnormal and unable to transfer their information varied depending on the number of repeats. Cells with genes with 182 or more repeats still made messenger RNA, but in reduced amounts. But the protein-building machinery couldn't handle what little RNA existed in cells with 266 or more repeats, she discovered.

These data show for the first time that the lack of fmr protein leads to fragile X syndrome. "He makes some protein but not enough," says Feng. Some researchers have sought ways to trick cells with these altered genes to make messenger RNA. But her results indicate that even then the cell may still fail to make functional protein.