New Gene Linked to Blindness in Children

July 31, 2012

Four research teams, including two funded by the Foundation Fighting Blindness, have found a new gene linked to Leber congenital amaurosis (LCA), a form of retinal degeneration that causes severe vision loss or blindness at birth. Known as NMNAT1, it is the 18th gene linked to LCA. By knowing the gene, researchers are better able to understand why defects in it cause vision loss. The knowledge also helps scientists identify potential targets for vision-saving treatments. Thus far, the researchers have determined that NMNAT1 ultimately plays a key role in maintaining cell health and metabolism.

The two Foundation-funded teams making the discovery were a collaborative group from the Massachusetts Eye and Ear Infirmary (MEEI), The Children’s Hospital of Philadelphia (CHOP) and Loyola University Chicago Health Sciences Division, as well as a team from Oregon Health & Science University.

The two other teams linking NMNAT1 to LCA were from the University of Tübingen in Germany and McGill University Health Centre in Montreal.

All the researchers used an innovative technique known as whole-exome sequencing to find the gene. The approach targets the genetic region where disease-causing defects are most likely to occur. Nearly 10 years ago, researchers had identified the general region on chromosome 1 for this LCA gene, but whole-exome sequencing enabled them to actually pinpoint it to NMNAT1.

The MEEI-CHOP-Loyola group initially found NMNAT1 in a family with two siblings affected by LCA. The researchers then screened an additional 284 people with LCA in the United States, England and France, and found that an additional 13 individuals had defects in NMNAT1 as the cause of their disease.

Dr. Eric Pierce, a co-senior investigator on the project from the MEEI and chairman of the Foundation’s Scientific Advisory Board, says that defects in NMNAT1 quickly lead to damage to the macula, the area of the retina responsible for central vision. However, if a treatment was delivered early enough, central vision loss could be spared.

“There are two key factors that led to this advancement,” says Dr. Stephen Rose, chief research officer, Foundation Fighting Blindness. “The first is the highly advanced technologies used for genetic screening. The second is the institutional collaboration — the researcher’s sharing information to more quickly and effectively advance the research. As a funding source for this effort, we are excited by the ingenuity of these teams to move us closer to sight-saving treatments and cures.”

All of the NMNAT1 findings were published online on July 29, 2012, in Nature Genetics.