Inherited Osteoarthropathy in Scottish Fold Cats Is Associated with Altered Calcium Channel Function

Inherited osteoarthropathy in human is characterized by an aggressive arthropathy of fingers and toes with shortening of the phalanges. Individuals that appear normal at birth are affected by severe arthropathy by adulthood. Scottish Fold cats are characterized by a folded ear phenotype. There is clinical, radiologic, histologic and genetic evidence that Scottish Fold cats have an underlying congenital defect affecting the structure and function of cartilage, resulting in progressive bone, joint and cartilage abnormalities that subsequently lead to progressive dysfunction. Pedigree analyses and breeding experiments proved the phenotype to be inherited as an autosomal monogenic dominant trait with variable expression in Scottish fold individuals. Cats with two copies of the mutated gene show a severe disease phenotype from an early age while heterozygote cats show symptoms that vary from mild to moderate in severity (in terms of extent of involvement and clinical progression). Different severity in phenotype could be due to environmental or genetic modifiers at different loci. A genome-wide association study performed using the Illumina 63K array data on 99 Scottish fold cats (44 cases and 55 controls), localized the trait to cat chromosome D3. Candidate gene screening identified a gene involved in osteoarthropathy, cartilage homeostatsis and skeletal dysplasias in humans. Gene analysis revealed a missense mutation within a calcium channel associated with the aesthetic and clinical phenotypes.