POSTER ABSTRACTS
HCM causative variants have been identified and diagnostic tests are widely used, helping prac- titioners 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. #37 Deletion in canine GLRA1 is associated with progressive hypertonia resembling human hyperekplexia Marjo K Hytönen1,2 , Tiina Heinonen1,2 ,Kaspar Matiasek3, Hanna Müller4, Alexandra Kehl5, Thomas Flegel6, Hannes Lohi1,2 marjo.hytonen@helsinki.fi 1University of Helsinki and 2Folkhälsan Research Center, Helsinki, Finland; 3Ludwig-Maximilians- Universität München (LMU Munich), Munich, Germany; 4Tieraerztliches Fachzentrum Muehlhausen Dr. Ortmann & Dr. Stief, Muehlhausen/Thueringen, Germany; 5LABOKLIN GmbH&CO.KG, Bad Kissingen, Germany; 6University of Leipzig, Leipzig, Germany We observed closely related Miniature Australian Shepherd puppies affected with episodic stiffness and subsequent collapse. The clinical signs progressed within a few months to permanent hyper- tonia and inability to ambulate. After the exclusion of known variants causing myotonia, we carried out whole genome sequencing and identified a 36-bp deletion in glycine receptor alpha 1 (GLRA1) segregating as a recessive disease in the pedigree. In silico analysis of the variant predicted exon skipping followed by a frameshift leading to a premature termination of the protein translation which would disable the protein function. GLRA1 encodes a glycine receptor subunit, which mediates postsynaptic inhibition in the central nervous system and the variants in the gene are known to cause hyperekplexia in humans. Hereditary hyperekplexia is a rare neurological disease characterized by sudden and exaggerated startle response to unexpected sensory stimulus, e.g. simple and intense tactile or auditory stimuli. This is followed by an episode of general body stiffen- ing with unaltered consciousness. The clinical features in affected dogs were similar, although not entirely identical to human condition. Two other variants in dogs are known to be associated with hyperekplexia, however this is the first likely pathogenic variant in canine GLRA1. The breed will benefit from genetic testing to prevent the disease and control the variant prevalence.
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