Biallelic MFSD8 variants are an established cause of severe late-infantile subtype of neuronal ceroid lipofuscinosis (v-LINCL), a severe lysosomal storage disorder, but have also been associated with nonsyndromic adult-onset maculopathy.
Juvenile neuronal ceroid lipofuscinosis (JNCL) is a lysosomal storage disease caused by autosomal recessive mutations in ceroid lipofuscinosis 3 (CLN3).
We have conducted proteomic analyses of brain and cerebrospinal fluid (CSF) from mouse models of the most frequently diagnosed NCL diseases: CLN1 (infantile NCL), CLN2 (classical late infantile NCL) and CLN3 (juvenile NCL).
CLN2 disease is a genetic disorder caused by dysfunction of the lysosomal enzyme tripeptidyl peptidase 1 (TPP1) that belongs to the neuronal ceroid lipofuscinoses (NCL) and leads to epilepsy, dementia, and death in young persons.
We have conducted proteomic analyses of brain and cerebrospinal fluid (CSF) from mouse models of the most frequently diagnosed NCL diseases: CLN1 (infantile NCL), CLN2 (classical late infantile NCL) and CLN3 (juvenile NCL).
Among them, a 12.4-kb deletion involving the CLN6 gene was the top candidate because its homozygous abnormalities cause neuronal ceroid lipofuscinosis.
Mutation of CLN6 has emerged as the most important cause of recessive Kufs disease but, remarkably, is also responsible for variant late infantile ceroid lipofuscinosis.
Because homozygous mutations in MFSD8 cause neuronal ceroid lipofuscinosis (NCL), similar to homozygous mutations in GRN, we assessed rare variants in MFSD8 for relevance to FTLD through experimental follow-up studies.
Additionally, compound heterozygous pathogenic variants of PPT1 gene were detected in a girl, who initially displayed typical RTT features, but progressed into neuronal ceroid lipofuscinoses (NCL) afterwards.
The responsible gene ATP13A2 was also associated with hereditary spastic paraplegia, uncomplicated early - or late-onset parkinsonism and a form of neuronal ceroid lipofuscinosis.
Neuronal ceroid lipofuscinosis (NCL) type 1 (CLN1) is a neurodegenerative storage disorder caused by mutations in the gene encoding the lysosomal enzyme palmitoyl-protein thioesterase 1 (PPT1).
However, the genetic spectrum of ATP13A2-associated disorders was expanded in the last years, because it has been found to underlay variants of neuronal ceroid-lipofuscinoses (NCLs) and hereditary spastic paraplegia.
We have conducted proteomic analyses of brain and cerebrospinal fluid (CSF) from mouse models of the most frequently diagnosed NCL diseases: CLN1 (infantile NCL), CLN2 (classical late infantile NCL) and CLN3 (juvenile NCL).
The two reported patients carrying novel pathogenic variants in KCTD7 gene presented with a remarkable phenotypic heterogeneity including: a) progressive myoclonus epilepsy without NCL-type lysosomal storages; b) progressive myoclonus epilepsy with lysosomal storages resembling NCL pattern (NCL14); c) progressive myoclonus epilepsy with epilepsia partialis continua.