For the second time in 2 months, scientists have reported the discovery of a gene linked to childhood glaucoma. This time, it's a gene for primary congenital glaucoma, a condition that strikes about 2000 infants and young children in the United States each year. The findings, described in next month's issue of Human Molecular Genetics, could lead to a genetic test, resulting in earlier diagnosis and treatment for a condition that can result in blindness.
Four years ago, Mansoor Sarfarazi and his colleagues at the University of Connecticut Health Center in Farmington began seeking out families with more than one member diagnosed with the condition, which is associated with a recessive gene. Linkage studies failed to find a candidate gene, so the group "started to screen the entire genome randomly," Sarfarazi says, eventually settling on chromosome 2. After months of grunt work ruling out genes, the group nailed their quarry: They linked mutations in a gene called CYP1B1 to the disease. Because cyp genes code for metabolic enzymes, Sarfarazi speculates that CYP1B1 codes for an enzyme that removes excess steroids, essentially functioning "as an antitoxin," he says.
The finding comes on the heels of a report last January of a gene linked to juvenile glaucoma, which strikes in the teenage years (ScienceNOW, 30 January ). These versions together account for less than 2% of total glaucoma cases, most of which develop in adulthood. The gene for juvenile glaucoma is expected to shed more light on the adult form, says Ellen Liberman of the National Eye Institute, because the subtle pathological changes in the eye in these forms are similar, while the congenital version is characterized by gross structural abnormalities.
Nevertheless, the discovery of the CYP1B1 gene could prevent thousands of cases of blindness each year in the United States and abroad--particularly, says Liberman, in countries "with a lot of first-cousin marriages" that tend to conserve recessive genes. "This is a very significant breakthrough which will provide a new dimension to neonatal care," says Jay Wisnicki, chair of ophthalmology at the Beth Israel Medical Center in New York. Indeed, a test for the defect could detect about 85% of newborns with the disease in afflicted families, estimates Kumar Chandrasekaran, chair of InSite Vision of Alameda, California, which holds the rights to license the discovery and develop a genetic test.