Scientists have isolated a gene that causes Leber's congenital amaurosis (LCA), a disorder that destroys its victims' vision within the first few months of life. The finding could someday lead to a cure for LCA, which is responsible for a few thousand cases of inherited blindness each year.
A team of French and American scientists at several institutes pinpointed mutations in the retinal guanylate cyclase (RETGC) gene in eight families in which the disease has struck. They report their findings in the December issue of Nature Genetics.
The scientists have an idea how the genetic error leads to retinal degeneration. In a normal retina, an enzyme cascade is activated when the retina processes light, and a second set of biochemical reactions takes place when the cells rest. A compound called cyclic GMP regulates this activity. But if the RETGC gene is flawed, cyclic GMP levels never reach those necessary to trigger the reactions that take place during the recovery stage. "This constant light causes the degradation of the retina," says Steven Pittler, a molecular biologist at the University of South Alabama in Mobile and one of the paper's authors.
The study is a "real landmark" because so little has been known about LCA, the only inherited disease of the retina that strikes early in childhood, says Samuel Jacobson, an ophthalmologist at the University of Pennsylvania's Sheie Eye Institute. Other experts are hailing the finding as the first step toward a cure or gene therapy for LCA. According to Gerald Chader, chief scientific officer for the Foundation Fighting Blindness in Baltimore, the discovery should "put Leber's right now into the forefront for genetic testing."