The strongest signal was observed at 16p12.1 (25 cM, 33 Mb; heterogeneity logarithm of odds = 5.3), ∼3 Mb upstream of the ceroid lipofuscinosis 3 (<i>CLN3</i>) gene associated with juvenile neuronal ceroid lipofuscinosis (JNCL), which functions in retromer trafficking and has been reported to alter intracellular processing of the amyloid precursor protein.
Ataxia is the major neuropathological finding in arylsulfatase G-deficient mice: similarities and dissimilarities to Sanfilippo disease (mucopolysaccharidosis type III).
We also discuss another ATP13A2 mutation that is associated with the family of neurodegenerative disorders called neuronal ceroid lipofuscinoses (NCLs), and we propose a single pathway whereby ATP13A2 mutations may contribute to NCLs and Parkinsonism.
To determine if loss of one functional Atp13a2 allele can serve as a risk factor for disease, we have now assessed heterozygous Atp13a2 knockout mice for key features of NCL.
The responsible gene ATP13A2 was also associated with hereditary spastic paraplegia, uncomplicated early - or late-onset parkinsonism and a form of neuronal ceroid lipofuscinosis.
Loss of function mutations in the gene ATP13A2 are associated with Kufor-Rakeb Syndrome and Neuronal Ceroid Lipofuscinosis, the former designated as an inherited form of Parkinson's disease (PD).
To see if ATP13A2 mutations could be responsible for some cases of human adult-onset NCL (Kufs disease), we resequenced ATP13A2 from 28 Kufs disease patients.
A mutation analysis for 14 positional candidate genes in two NCL-cases and one control revealed a strongly associated single nucleotide polymorphism (SNP) in the MAPK PM20/PM21 gene and a perfectly with NCL associated single base pair deletion (c.1620delG) within exon 16 of the ATP13A2 gene.
We present a family with typical NCL pathology in which we performed exome sequencing and identified a single homozygous mutation in ATP13A2 that fully segregates with disease within the family.
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.
Until now, fourteen mutations in ATP13A2 have been associated with KRS, while other mutations have been reported in association with neuronal ceroid lipofuscinosis (NCL) and early-onset PD.
The neuronal ceroid-lipofuscinosis (NCL) are a heterogeneous group of neurodegenerative diseases characterized by the lysosomal accumulation of ceroid and lipofuscin with mitochondrial ATP synthase subunit C in various tissues.
Our results showed that annexin A1, annexin A2, and vimentin were significantly down-regulated in NCL1, NCL2, NCL3, and NCL8 cells; galectin-1 was down-regulated in NCL1, NCL3, and NCL8 but up-regulated in NCL2 cells; and isoform 5 of caldesmon was up-regulated in all NCL cell types.
In neutral conditions, pH 6.0, the PPT1 enzyme activities in NCL 1 patients showed rather higher residual activities and intermediate activities in heterozygotes in NCL 1, which was probably caused by mutated proteins in three cases with NCL 1 patients.
Neuronal ceroid lipofuscinoses type I and type II (NCL1 and NCL2) also known as Batten disease are the commonly observed neurodegenerative lysosomal storage disorder caused by mutations in the PPT1 and TPP1 genes respectively.
Neuronal ceroid lipofuscinoses type I and type II (NCL1 and NCL2) also known as Batten disease are the commonly observed neurodegenerative lysosomal storage disorder caused by mutations in the PPT1 and TPP1 genes respectively.