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Leading reason for corneal transplants comes into focus

Guided by families with an unusual number of cases, scientists at Johns Hopkins have discovered the genetic origins of at least one form of Fuchs corneal dystrophy, FCD, the leading reason for corneal transplantation in the United States.

In one form or another, FCD's trademark deterioration of the cells covering the clear, outermost lens of the eye affects more than 4 percent of the population over 40. Late in life, the dystrophy causes swelling of the cornea and can severely affect vision, making it impossible to see well even with glasses or contact lenses. It's believed that various forms of FCD are due to multiple gene mutations.

In a report in the September issue of Investigative Ophthalmology, a team led by Hopkins ophthalmologist John Gottsch, M.D., says they were able to map a common form of Fuchs, found most often in women, to chromosome 18.

"Finding this chromosomal locus is putting us in the right neighborhood to find culprit genes," says Gottsch. "Now we have to start knocking on every door."

Gottsch is heartened by success with earlier Fuchs gene-hunting studies. The Hopkins group tracked down its first FCD-related gene in a Virginia family with multiple, early onset cases. That gene, labeled COL8A2, was mapped to chromosome 1.

Prior to that, a large Indiana family with FCD, including a boy of 10, led the team to yet another gene variant, on chromosome 13.

The scientists use linkage analysis, a process-of-elimination gene-hunting technique that analyzes inheritance patterns in families with relatively large numbers of affected individuals and trace genetic traits co-inherited or "linked" with the disorder. Researchers search for a common location for all the linked traits until they wind up with a single chromosome address.

In his latest study, Gottsch used not only linkage analysis but also a method of identifying variations in DNA sequences to examine three FCD families in which
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Source:Johns Hopkins Medical Institutions


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