A pathogenic HEXA missense variant in wild boars with Tay-Sachs disease

摘要: Abstract Gangliosidoses are inherited lysosomal storage disorders caused by reduced or absent activity of either a enzyme involved in ganglioside catabolism, an activator protein required for the proper hydrolase, which results intra-lysosomal accumulation undegraded metabolites. We hereby describe morphological, ultrastructural, biochemical and genetic features GM2 gangliosidosis three captive bred wild boar littermates. The piglets were kept partially-free range farm presented progressive neurological signs, starting at 6 months age. Animals euthanized approximately one year age due to their poor conditions. Neuropathogens excluded as possible cause signs. Gross examination showed reduction cerebral cerebellar consistency. Central (CNS) peripheral (PNS) nervous system neurons enlarged foamy, with severe diffuse cytoplasmic vacuolization. Transmission electron microscopy (TEM) CNS demonstrated numerous lysosomes, filled parallel concentric layers membranous electron-dense material, defined bodies (MCB). Biochemical composition gangliosides analysis from revealed ganglioside; furthermore, Hex A was less than 1% compared control animals. These data confirmed diagnosis gangliosidosis. Genetic identified, homozygous level, presence missense nucleotide variant c.1495C > T (p.Arg499Cys) hexosaminidase subunit alpha gene (HEXA), located within GH20 superfamily domain encoded protein. This specific HEXA is known be pathogenic associated Tay-Sachs disease humans, but has never been identified other animal species. first report boars thus provides comprehensive description novel spontaneous model this disease.