Common mutation found to cause congenital stationary night blindness in European and American briards; DNA test to be available by end of 1998

ITHACA, N. Y.--The discovery of the mutation responsible for a recessively inherited retinal disorder of briard dogs, congenital stationary night blindness (csnb), has led to the development at Cornell of a blood test to identify those dogs that carry or are affected by the disorder. The work was done in the laboratory of Dr. Gustavo Aguirre, VMD, PhD, the Caspary Professor of Ophthalmology at the James A. Baker Institute for Animal Health in the College of Veterinary Medicine.

Csnb is characterized by congenital night blindness and varying degrees of visual impairment, sometimes severe, in lighted conditions. The disease was initially described in Swedish briards as a stationary condition. More recently, however, studies in Swedish pedigrees revealed a progressive component to the condition, prompting it to be characterized as a hereditary retinal dystrophy. A research group in Europe recently reported finding the cause of retinal dystrophy in the Swedish briards, a mutation in the retinal pigment epithelium gene RPE65.

Outside of the briards in the Swedish study, there has been no systematic study of retinal dystrophy in dogs and no definitive proof that csnb and retinal dystrophy represent the same disorder. The Aguirre group cloned and sequenced the RPE65 gene in the briards in which they had been studying csnb. This was done to look for a possible correlation between the retinal dystrophy mutation and csnb. The dogs in the Cornell study originated from stock in the United States, Canada, and France. Dr. Aguirre and his associates found the mutation was present in all the briards they tested that were known to have csnb and confirmed that each of the obligate carriers from those same pedigrees had one copy each of the normal and mutated gene sequences. They next tested Swedish dogs with csnb and found that they, too, had the same mutation. Those and further studies at the Institute confirmed that the American disease, csnb, and the Swedish disease, retinal dystrophy, represent the same disorder in briards. Furthermore, since some of the dogs tested were apparently unrelated, the discovery of a common mutation in lines originating in different countries suggests a founder effect causing the propagation of a common defect.

Dr. Aguirre's group has now followed up this work by developing a mutation-based blood test to determine with complete reliability the csnb status--whether normal, carrier, or affected--of any briard from any pedigree. The test is expected to be available by the end of 1998.

Other members of the Aguirre laboratory who participated in these studies were senior research associates Dr. Gregory Acland and Dr. Kunal Ray, research support specialist Sue Pearce-Kelling, and technician Victoria Baldwin. Dr. Kristina Narfstrom of the Swedish University of Agricultural Sciences in Uppsala also collaborated with the Cornell group.

Partial funding for this study was provided by the Briard Club of America, the American Kennel Club Canine Health Foundation, Morris Animal Foundation / The Seeing Eye, the Foundation Fighting Blindness, and the National Eye Institute of the NIH. The authors are grateful to the many owners and breeders who willingly participated in this study by making their dogs available to the investigators.