Here, we summarize the current understanding of the thirteen identified NCL genes and the proteins they encode, touching upon the spectrum of clinical manifestations linked to each of the genes, and we highlight recent progress leading to a broader understanding of key pathways involved in NCL disease pathogenesis and commonalities with other neurodegenerative diseases.
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.
To date 13 sequence variants in 8 canine orthologs of human NCL genes have been found to occur in 11 dog breeds in which they result in progressive neurological disorders similar to human NCLs.
14 different genes have been linked to NCLs (CLN1-CLN14), but the functions of the proteins encoded by the majority of these genes have not been fully elucidated.
In this review we will chronologically summarise work which has led over the years to identification of NCL genes, and outline the potential of novel genomic techniques and related bioinformatic approaches for further genetic dissection and diagnosis of NCLs.
We report our linkage data on a family with late-infantile NCL and show that the disease in this family is due to a homozygous novel mutation in the most recently described NCL gene (MFSD8).