The NCLs include eight forms that result from genetic deficiency on genes CLN(1) to CLN(8), respectively: four classic forms with clinical onset at varying ages-infantile (INCL), late-infantile (LINCL), juvenile (JNCL), and adult (ANCL)-and four variants of late-infantile onset-the Finnish variant LINCL (fLINCL), Portuguese variant LINCL (pLINCL), Turkish variant LINCL (tLINCL), and progressive epilepsy with mental retardation (EPMR).
The late-infantile-onset forms of neuronal ceroid lipofuscinosis (LINCL) are the most genetically heterogeneous group among the autosomal recessive neuronal ceroid lipofuscinoses (NCLs), with causative mutations found in CLN1, CLN2, CLN5, CLN6, CLN7 (MFSD8), and CLN8 genes.
A homozygous mutation in the orthologous mouse gene (Cln8) underlies the phenotype of a naturally occurring NCL model, the motor neuron degeneration mouse (mnd).
CLN8 mutation was first identified in Finnish patients, and the condition was named Northern Epilepsy (NE); however, the severe phenotype of the CLN8 gene was subsequently found outside Finland and named 'variant late-infantile' NCL.
Our data indicate that patients with clinical signs of late infantile NCL and characteristic ultrastructural inclusions should also be screened for CLN8 mutations independent of their ethnic origin.
Here we present two confirmed cases of NCL in Alpenländische Dachsbracke dogs from different litters of the same sire with a different dam harboring the same underlying novel mutation in the CLN8 gene.