Mutations in CLN6 were recently identified in recessive Kufs disease presenting as progressive myoclonus epilepsy (Type A), whereas the molecular basis of cases presenting with dementia and motor features (Type B) is unknown.
None of these patients had ATP13A2 sequence variants likely to be causal for their disease, suggesting that mutations in this gene are not common causes of Kufs disease.
We subsequently sequenced CTSF in 22 unrelated individuals with suspected recessive Kufs disease, and identified an additional patient with compound heterozygous mutations.
Here, we report a sporadic case of Kufs disease type B with novel compound heterozygous mutations, a novel missense mutation c.977G>T (p.C326F) and a novel nonsense mutation c.416C>A (p.S139X), in the cathepsin-F gene.
Our findings provide evidence that LIMP-2 represents an in vivo substrate of cathepsin-F with relevance for understanding the pathophysiology of type-B-Kufs-disease.
In silico analysis of mutation p.Leu(381)Phe predicted more detrimental effects when compared to the common Presenilin 1 mutation p.Glu(280)Ala. Electron microscopy study of peripheral fibroblast cells of the proband showed lysosomal inclusions typical for Kufs disease.
Our findings provide evidence that LIMP-2 represents an in vivo substrate of cathepsin-F with relevance for understanding the pathophysiology of type-B-Kufs-disease.
Autosomal dominant adult neuronal ceroid lipofuscinosis: a novel form of NCL with granular osmiophilic deposits without palmitoyl protein thioesterase 1 deficiency.