Genetic innovations by Medical Center researchers have taken a large step toward solving the mystery of an eye disease that affects only a small population of North Carolinian Native Americans.
Now that the researchers have pinpointed a duplication on chromosome four that causes hereditary benign intraepithelial dyskeratosis, which is experienced only by a Native American tribe from the mountains of northeastern North Carolina, they will begin to look for the specific gene that is linked to it.
"We are pretty confident about finding the actual gene responsible for this disease because we've localized the area, and it's just a matter of time before we identify a candidate gene," said Dr. Pratap Challa, assistant professor of ophthalmology and a member of the research team performing a follow-up study.
HBID often interferes with normal vision, produces red or bloodshot eyes in the affected and, in extreme cases, causes blindness. The National Institutes of Health first investigated this disease in the 1960s but did not reach any definitive conclusions. Afflicted individuals, though, began coming to the Duke Eye Center for treatment in the '90s. Now, only a few treatments, including temporary surgical removal of the eye plaque caused by HBID, are available to patients.
This rare eye disease also exhibits what researchers call the "founder's effect," where gene mutations of one person are passed on to future generations.
"Founder's effect is seen where an individual has a mutated gene that is present in all extending offspring. It is best observed in [people living in] areas of circumscribed regions like islands, or in this case, within certain populations," said Dr. Rand Allingham, associate professor of ophthalmology and the study's co-investigator. "However, it is not clear where the gene for HBID originated from or what the initial mutation was caused by."
HBID is characterized by plaque-or abnormal growth-formation on the mucosal linings of the eyes and mouth. Although benign, the rapid proliferation of epithelial cells caused by HBID resembles the effects of cancer, providing compelling motivation for the study of HBID.
"There may be a common point of origin in multiple diseases that cause cell proliferation," said Challa, explaining the study's applicability to other disorders.
For the past three-and-a-half years, the researchers collected and conducted detailed genetic analyses on more than 350 blood samples from members of two large families that exhibited HBID. In 25 people who showed symptoms of HBID, researchers noticed two distinct markers near the end of chromosome four that were common to all.
These findings also provide a good way to study founder's effect because cultural factors have confined the genetic mutation to a specific geographic location. Every known case of HBID, with the exception of a disputed case reported in Texas, has occurred in descendants of the North Carolina tribe.
"An increased knowledge of genetics can come through studying these families even though this is a rare disease," said Dr. Jeffery Vance, associate professor of neurology and medicine and also the principal investigator of this study.
Now that researchers have pinpointed the chromosome responsible for HBID, they are currently designing tests to identify the specific gene and refine the observations made in clinical trials.
"We know that the gene responsible for HBID somehow controls cell growth, so once we identify the gene that's involved, it will add to our knowledge of epithelial cells and their development," Challa said.
The study was funded by the National Eye Institute of the National Institutes of Health and was presented to the American Society for Human Genetics earlier this month. A paper was also submitted to the American Journal of Human Genetics for review.
"This may not be cancer or heart disease work, but for the people affected by this disease, this is really important research," Allingham said.
Get The Chronicle straight to your inbox
Signup for our weekly newsletter. Cancel at any time.