Neuronal ceroid lipofuscinoses (NCLs) are heterogenic inherited lysosomal storage diseases that have been described in a number of species including humans, sheep, cattle, cats and a number of different dog breeds, including Salukis. Here we present a novel genetic variant associated with the disease in this particular breed of dog. In a clinical case, a Saluki developed progressive neurological signs, including disorientation, anxiety, difficulties in eating, seizures and loss of vision, and for welfare reasons, was euthanized at 22 months of age. Microscopy showed aggregation of autofluorescent storage material in the neurons of several brain regions and also in the retina. The aggregates showed positive staining with Sudan black B and periodic acid Schiff, all features consistent with NCL. Whole genome sequencing of the case and both its parents, followed by variant calling in candidate genes, identified a new variant in the CLN8 gene: a single bp insertion (c.349dupT) in exon 2, introducing an immediate stop codon (p.Glu117*). The case was homozygous for the insertion, and both parents were heterozygous. A retrospective study of a Saluki from Australia diagnosed with NCL identified this case as being homozygous for the same mutation. This is the fourth variant identified in CLN8 that causes NCL in dogs.
Keywords: dog; lysosomal storage disease; mutation; stop codon; whole genome sequencing.
© 2017 Stichting International Foundation for Animal Genetics.