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.
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.
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.
It displays 82% nucleotide identity with CLN8, conservation of the codon harbouring the human mutation and is localized to the same region as the motor neuron degeneration mouse, mnd, a naturally occurring mouse NCL (ref.4).
Patients with CLN8 mutations usually present as the late-infantile-onset neuronal ceroid lipofuscinosis phenotype and are mostly Turkish and Italian, but three patients from Israel, Pakistan, and Germany were also reported.
Although functions are defined for some of the soluble proteins that are defective in NCL (cathepsin D, PPT1, and TPP1), the primary function of the other proteins defective in NCLs (CLN3, CLN5, CLN6, CLN7, and CLN8) remain poorly defined.