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).
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.
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.
In five of the eight NCL variants distinguished at present, genes associated with the disease process have been isolated and characterized (CLN1, CLN2, CLN3, CLN5, CLN8).
Neuropathological findings have shown that EPMR is a new member (CLN8) of the neuronal ceroid lipofuscinosis (NCL) group of neurodegenerative disorders.The CLN8 gene was identified recently.
Neuronal ceroid lipofuscinoses (NCL) comprise the most common group of childhood encephalopathies caused by mutations in eight genetic loci, CLN1-CLN8.
We report the first known case in Israel of a patient with an early childhood onset of ceroid-lipofuscinosis who is homozygous to a mutation of the CLN8 gene.
Our findings expand the variant diversity of CLN8 and demonstrate the tremendous diagnosis value of targeted next-generation sequencing for pediatric NCLs.
Loss of function mutations in CLN8 causes neuronal ceroid-lipofuscinosis, but our results indicate that its increased expression may protect against severe GD1.