Louisiana Family Helps Lead to Discovery of New RP Gene

September 17, 2014

A new gene linked to autosomal dominant retinitis pigmentosa (adRP) has been identified, thanks to a Foundation Fighting Blindness-funded genetic study that began with an Acadian family from Louisiana whose vision loss can be traced back to the early 1800s. Led by Stephen Daiger, Ph.D., at the University of Texas Health Science Center in Houston, an international research collaborative found that mutations in the gene HK1 cause adRP in the family, which provided blood or saliva samples from 19 of its members for genetic screening.

Subsequently, the researchers found HK1 mutations as the cause of adRP in two other families in Louisiana as well as families in Canada and Sicily. A total of 404 people were screened in the study. Ultimately, the discovery will help doctors diagnose more patients with adRP and identify targets for vision-saving treatments. Results of the study were published in the journal Investigative Ophthalmology & Visual Science.

Early on, the study focused on the Acadian family because of its long history of vision loss and the number of family members affected. Acadians are descendants of the French who settled in Eastern Canada during the 1700s. Many later migrated to what is now Louisiana.

“Because retinal diseases are genetic, they run in families and populations with common ancestries, including Ashkenazi Jews, Northern Europeans and certain populations from the Middle East and Asia,” explains Stephen Rose, Ph.D., the Foundation’s chief research officer. “That makes family-based studies like Dr. Daiger’s invaluable in the search for new genes causing vision loss.”

Dr. Daiger says new tools that search for disease-causing mutations in regions of DNA where they are most likely to occur are more quickly and efficiently leading to discoveries. Also, collaboration with other scientists plays a critical role in achieving success.

“Long-term, cooperative relationships with world-class researchers are essential to these studies,” Dr. Daiger says. “By pooling our patients together, we greatly increase our chances of finding new retinal-disease genes.” The HK1 study included investigators from the United Kingdom, Canada and the United States.

Dr. Daiger and his collaborators estimate that the mutation in HK1 accounts for approximately one percent of all adRP cases in Europeans and Americans of European origin. Mutations in approximately 70 genes are known to cause retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), a severe form of the condition causing loss of vision at birth.

Dr. Daiger’s laboratory, which has been funded by the Foundation for nearly three decades, focuses on the search for gene mutations that cause adRP. Work in his lab has led to the discovery of seven genes linked to RP: HK1, RP1, AIPL1, IMPDH1, KLHL7, BBS8 and SNRNP200. Most forms of RP cause progressive vision loss starting in childhood or adolescence. Those affected initially experience night blindness and loss of peripheral vision.

Most are legally blind by the age of 40. A person with the autosomal dominant form of RP or other dominant genetic diseases has a 50-percent chance of passing the condition down to each child. Other Foundation articles on Dr. Daiger and his genetic research include:

ARVO 2014: Breaking the 50-Percent Barrier in Successful Genetic Screenings

RetNet: A Web-Based Guide to Every Retinal Disease Gene Known to Man

Your Gene is Their Business

Looking for Genes in All the Right Places