Rett syndrome is the first disease shown to result from defects in a protein that silences other genes, Francke said. Diagnosing the disorder before the child is four or five years old is often very difficult, Francke said. One of the first payoffs from this discovery will be a genetic test to improve the accuracy of early diagnosis. If combined with an effective therapy, the test might allow doctors to ameliorate or forestall the drastic consequences of the disease. Because of differences in the sex chromosomes, girls can survive with Rett syndrome, while affected males die before or shortly after birth, Francke explained.
Females have two X chromosomes, but only one is active in any particular cell.
That means that only about half of the cells in a girl's nervous system will actually be using the defective gene. But males have a single X chromosome, so all of their cells are obliged to use the faulty version of the gene, a situation that presumably results in fatal defects. The other Stanford co-author on the paper is Mimi Wan, MD, PhD, a postdoctoral fellow in Francke's lab. Funding for the work came from the Howard Hughes Medical Institute, the National Institutes of Health, the International Rett Syndrome Association, the Society for Gynecologic Investigation and the L.M. Chandler Research Fund.