A mixed breed dog with neuronal ceroid lipofuscinosis is homozygous for a CLN5 nonsense mutation previously identified in border collies and Australian cattle dogs

Publication date: Available online 17 April 2019Source: Molecular Genetics and MetabolismAuthor(s): Natalie A. Villani, Garrett Bullock, Jennifer R. Michaels, Osamu Yamato, Dennis P. O'Brien, Tendai Mhlanga-Mutangadura, Gary S. Johnson, Martin L. KatzAbstractThe neuronal ceroid lipofuscinoses (NCLs) are a group of inherited neurodegenerative disorders characterized by progressive declines in neurological functions following normal development. The NCLs are distinguished from similar disorders by the accumulation of autofluorescent lysosomal storage bodies in neurons and many other cell types, and are classified as lysosomal storage diseases. At least 13 genes contain pathogenic sequence variants that underlie different forms of NCL. Naturally occurring canine NCLs can serve as models to develop better understanding of the disease pathologies and for preclinical evaluation of therapeutic interventions for these disorders. To date 14 sequence variants in 8 canine orthologs of human NCL genes have been found to cause progressive neurological disorders similar to human NCLs in 12 different dog breeds. A mixed breed dog with Labrador Retriever and Beagle parents developed progressive neurological signs consistent with NCL starting at approximately 11 to 12 months of age, and when evaluated with magnetic resonance imaging at 21 months of age exhibited diffuse brain atrophy. Due to the severity of neurological decline the dog was euthanized at 23 months of age. Cerebellar and ...
Source: Molecular Genetics and Metabolism - Category: Genetics & Stem Cells Source Type: research