Allele drop-out cases in screening of HCM associated ALMS1 gene variant in Italian Sphynx cats

(#36) Hypertrophic cardiomyopathy (HCM) is the most common cardiomyopathy in domestic cats. Several clinical forms have been identified and both classification and differentiation from normal variation are still often difficult. In pure breeds (Maine Coon, Ragdoll, and Sphynx) and random-bred cats HCM causative variants have been identified and diagnostic tests are widely used, helping practitioners in prognosis and breeders in selection. However, when clinical and genetic screening of known variants have been carried out on different populations, differences in penetrance and expressivity have been reported, suggesting an effect of different genetic backgrounds on HCM onset and development, and supporting the use of both clinical and genetic investigations, for more accurate knowledge, classification, and management of the disease. Since 2006, the Osservatorio Italiano Veterinario Cardiopatie (OVIC) has been storing clinical and genetic data, pedigrees, and tissues (maintained at the “Animal Bio Arkivi”, a repository of the University of Milan, Lodi, Italy) and promoting periodic analysis of data collected for genetic consulting, in partnership with University and service labs. Screening has been recently conducted on the identified HCM-associated ALMS1 gene variant in the Sphynx breed (Meurs K. et al, 2021) on OVIC present and archive Sphynx samples. Nucleotide variability in flanking regions has been observed using Sanger sequencing. Thanks to clinical data, pedigrees, and trio samples availability, an allele drop-out of the wild-type allele have been identified in cats unrelated in the fourth generation. Allele frequency analysis is showing a fairly wide diffusion of the variant in the Sphynx population bred in Italy.