Role of an1930_1931del TC gene mutation in a temporal cluster of macrocyclic lactone-induced neurologic toxicosis in cats associated with products labeled for companion animal use.

Abstract

OBJECTIVE: To determine whether1930_1931del TC predisposed cats to macrocyclic-lactone toxicosis and the frequency of the1930_1931del TC gene mutation in banked feline DNA samples. SAMPLE: DNA samples from 5 cats presented for neurologic clinical signs presumed to be caused by exposure to macrocyclic lactones and 1,006 banked feline DNA samples. PROCEDURES: The medical history pertaining to 5 cats was obtained from veterinarians who examined, treated, or performed necropsies on them. The DNA from these 5 cats and 1,006 banked feline samples were analyzed for the presence of the1930_1931del TC genotype. RESULTS: 4 of the 5 cats with neurologic signs presumed to be associated with macrocyclic-lactone exposure were homozygous for1930_1931del TC. The other cat had unilateral vestibular signs not typical of macrocyclic-lactone toxicosis. The distribution of genotypes from the banked feline DNA samples was as follows: 0 homozygous for1930_1931del TC, 47 heterozygous for1930_1931del TC, and 959 homozygous for the wild-typeallele. Among the 47 cats with the mutantallele, only 3 were purebred (Ragdoll, Russian Blue, and Siamese). CONCLUSIONS AND CLINICAL RELEVANCE: Results suggested a strong relationship between homozygosity for1930_1931del TC and neurologic toxicosis after topical application with eprinomectin-containing antiparasitic products labeled for use in cats. Although this genotype is likely rare in the general cat population, veterinarians should be aware of this genetic mutation in cats and its potential for enhancing susceptibility to adverse drug reactions.