Researchers ID genetic mutation associated with high risk of age-related macular degeneration

Contact: Lori Shanks
ljshanks@partners.org
617-534-1604
Brigham and Women's Hospital
Researchers ID genetic mutation associated with high risk of age-related macular degeneration

Investigators show a specific rare mutation called CFH R1210C that predicts a very high risk of disease
Boston, MA – Age- related macular degeneration (AMD) is the leading cause of severe visual loss among the elderly. Researchers had previously identified several relatively common genetic variants which together predict a person's increased risk for AMD, but a significant number of persons without the disease also have these variants. Now, for the first time, investigators have been able to clearly show a specific rare mutation called CFH R1210C that predicts a very high risk of disease and is extremely uncommon among individuals who do not have the disease. Although it is a rare variant, accounting for about 1% of the total cases, it is highly related to familial disease and earlier age of onset. This research is published online and in an upcoming print edition of Nature Genetics. The paper is a collaborative effort between investigators from Tufts Medical Center, Tufts University School of Medicine and Brigham and Women's Hospital.

"Our paper shows that there is a genetic variant that confers high risk of the development of AMD; this finding not only clearly links CFH gene dysfunction to disease, but also might help to identify people who need to be screened more closely," said first author, Soumya Raychaudhuri, MD, PhD, a researcher in the Divisions of Genetics and Rheumatology at Brigham and Women's Hospital and an Assistant Professor of Medicine at the Harvard Medical School.

Prior to this publication, it was known that genetic variation within the CFH gene influenced risk of AMD in individuals. In this study, researchers conducted sequencing and genotyping of CFH in 2,423 AMD cases and 1,122 controls in the laboratory of senior author Johanna M. Seddon, MD, ScM, Professor of Ophthalmology at Tufts University School of Medicine and Director of the Ophthalmic Epidemiology and Genetics Service at Tufts Medical Center. They identified a rare, high-risk mutation resulting in an arginine to cysteine substitution in the CFH protein. This mutation is associated with loss of function of the CFH protein and its discovery suggests that loss of CFH function can drive AMD risk. It was associated with advanced AMD with visual loss and many of the patients also had numerous drusen, which are the early hallmarks of AMD.

"The discovery of this rare but penetrant variant strongly associated with disease also points the way to developing new and effective treatments for high risk individuals," said Seddon.

Collaborators in this research included investigators from Massachusetts General Hospital and Johns Hopkins University.

###

This research was supported by an anonymous donor; the National Institutes of Health (NIH); the Massachusetts Lions Eye Research Fund, Inc.; the Macular Vision Research Foundation; a Research to Prevent Blindness Challenge Grant to the New England Eye Center, Department of Ophthalmology, Tufts University School of Medicine; and the Macular Degeneration Research Fund of the Ophthalmic Epidemiology and Genetics Service, New England Eye Center, Tufts Medical Center and Tufts University School of Medicine.

About Brigham and Women's Hospital
Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is the home of the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), www.brighamandwomens.org/research , BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 900 physician-investigators and renowned biomedical scientists and faculty supported by more than $537 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit http://www.brighamandwomens.org/.

About Tufts Medical Center
Tufts Medical Center is an exceptional, not-for-profit, 415-bed academic medical center that is home to both a full-service hospital for adults and Floating Hospital for Children. Located in downtown Boston, the Medical Center is the principal teaching hospital for Tufts University School of Medicine. New England Eye Center (NEEC), the ophthalmology department for Tufts Medical Center and Tufts University School of Medicine, offers a full range of comprehensive ophthalmology including treatments for cataracts, glaucoma, macular degeneration, pediatric ophthalmology and aesthetic surgery. NEEC is also a leading provider of Laser Vision Correction in Greater Boston and New England offering a full range of vision correction procedures for all types of eye conditions. Floating Hospital for Children is the full-service children's hospital of Tufts Medical Center and the principal pediatric teaching hospital of Tufts University School of Medicine. Tufts Medical Center is affiliated with seven community hospitals and with New England Quality Care Alliance, its community physicians' network. Tufts Medical Center has been ranked by University Health Systems Consortium as one of the top tier academic medical centers in the country. For more information, please visit http://www.tuftsmedicalcenter.org/ and http://www.neec.com/.

Researchers ID genetic mutation associated with high risk of age-related macular degeneration