Anesthesia in a child with batten disease. (2004 Sep)
anesthesia in a child with batten disease .

Molecular basis of the neuronal ceroid lipofuscinoses : mutations in CLN1 , CLN2 , CLN3 , and CLN5. (1999 Oct)
molecular basis of the neuronal ceroid lipofuscinoses : mutations in CLN1 , CLN2 , CLN3 , and CLN5 . The neuronal ceroid lipofuscinoses ( NCLs ) , also referred to as batten disease , are a group of neurodegenerative disorders characterised by the accumulation of an autofluorescent lipopigment in many cell types . different NCL types are distinguished according to age of onset , clinical phenotype , ultrastructural characterisation of the storage material , and chromosomal location of the disease gene . At least eight genes underlie the NCLs , of which four have been isolated and mutations characterised : CLN1 , CLN2 , CLN3 , CLN5 . Two of these genes encode lysosomal enzymes , and two encode transmembrane proteins , at least one of which is likely to be in the lysosomal membrane . The basic defect in the NCLs appears to be associated with lysosomal function .

Progress towards understanding the neurobiology of batten disease or neuronal ceroid lipofuscinosis. (2003 Mar)
progress towards understanding the neurobiology of batten disease or neuronal ceroid lipofuscinosis . purpose OF review : The identification of genes mutated in the neuronal ceroid lipofuscinoses has accelerated research into the mechanisms that underlie these fatal autosomal recessive storage disorders , which are often referred to as batten disease . This review summarizes progress in this field since october 2001 , describing advances in cell biology , the characterization of new animal models of neuronal ceroid lipofuscinosis , and the impact of novel methodology to reveal insights into its pathogenesis . recent findings : Gene products for six of the eight forms of neuronal ceroid lipofuscinosis have now been discovered , and concerted efforts are underway to understand the normal biology of each gene product and how this may be altered by mutation . several lines of evidence point to functions for the CLN genes in the endosomal lysosomal system , and suggest neuron specific roles for these proteins . indeed , a requirement for appropriate protein trafficking within neurons may explain the profound and selective effects of these disorders upon the central nervous system . The development of mouse and large animal models has enabled comparative studies of the progressive effects of disease , including characterization by morphological and biochemical means supplemented by metabonomic and microarray techniques . summary : insights into disease mechanisms are building a detailed profile of the impact of neuronal ceroid lipofuscinosis upon the brain . With the eventual aim of developing successful therapeutic …

The value of positron emission tomography in the diagnosis and monitoring of late infantile and juvenile lipopigment storage disorders ( … (1997 Aug)
The value of positron emission tomography in the diagnosis and monitoring of late infantile and juvenile lipopigment storage disorders ( so called batten or neuronal ceroid lipofuscinoses ) . positron emission tomography ( PET ) with 2 deoxy 2 18F fluoro D glucose provides a measure of functional brain activity , particularly in the dendritic field . In CLN3 ( juvenile neuronal ceroid lipofuscinosis or juvenile batten disease , with fingerprint inclusions ) hypometabolism slowly spreads from calcarine to anterior areas , sparing subcortical structures and brainstem . In CLN2 ( late infantile neuronal ceroid lipofuscinosis or jansky bielschowsky disease , with curvilinear inclusions ) degeneration is rapid with generalized cortical and subcortical hypometabolism . This is associated with rapidly progressive cerebral atrophy on anatomical neuroimaging . A 4 year old child with CLN2 scanned with PET 13 months after the clinical onset showed hypometabolism , severe in the thalamus and mild in cortical areas . three other patients with CLN2 had severe generalized hypometabolism and brain atrophy . longitudinal PET studies in CLN may provide key insights into degenerative processes .

Translocation 10 ; 18 in a patient with juvenile neuronal ceroid lipofuscinosis ( batten disease ). (1995 Oct)
translocation 10 ; 18 in a patient with juvenile neuronal ceroid lipofuscinosis ( batten disease ) . We report the first observation of a chromosome abnormality in a patient with typical juvenile ceroid lipofuscinosis ( NCL ) , who was found to have an apparently balanced translocation between chromosomes 10 and 18 t ( 10 ; 18 ) ( q22 . 1 ; q21 . 1 ) . since juvenile NCL was previously mapped to 16p12 , this report raises the possibility of heterogeneity in this form of NCL .

Linkage analysis in juvenile neuronal ceroid lipofuscinosis. (1992 Jul)
linkage analysis in juvenile neuronal ceroid lipofuscinosis . neuronal ceroid lipofuscinosis ( NCL , batten disease ) is an autosomal recessive disease characterized by progressive mental retardation , cortical atrophy , seizures , and retinal degeneration . several subtypes have been delineated on the basis of age at onset and histological characteristics ; the most common is the juvenile ( JNCL ) form . recently , the gene for JNCL was shown to reside on chromosome 16 through linkage studies to the haptoglobin locus and anonymous DNA markers using numerous european families . We have now examined 8 families from north america with JNCL for linkage to markers in 16q21 23 . results in 3 families tend to support linkage to chromosome 16 ; 3 families remained uninformative , and 2 families produced negative lod scores in this region . A test of homogeneity was suggestive , but could not significantly reject the null hypothesis of homogeneity . We are continuing to collect families , particularly those with multiple living affecteds , and are identifying other probes in this region . given close localization on chromosome 16 for JNCL , molecular strategies , including candidate gene strategies , are being explored .

Tissue and cellular distribution of subunit c of ATP synthase in batten disease ( neuronal ceroid lipofuscinosis ). (1995 Oct)
tissue and cellular distribution of subunit c of ATP synthase in batten disease ( neuronal ceroid lipofuscinosis ) . The major protein component of the storage bodies in the late infantile ( LIB ) and juvenile ( JB ) forms of batten diseases is subunit c of ATP synthase ( subunit c ) . ultrastructurally the stored material may appear as curvilinear bodies , fingerprint profiles , or a mixture of both , dependent upon the form of batten disease and the cell type . The mnd / mnd mouse , an animal model for batten disease , also stores subunit c and has loosely stacked lamellae within the neurons of the brain and in other cells and tissues . using a range of tissue samples , immunolocalization , using avidin biotin techniques at the LM level and postembedding immunogold labelling ( 5 nm ) with silver enhancement at the EM level , were used to investigate specific subunit c immunoreactivity . subunit c storage was displayed in a number of cells , including neurons , muscle cells , adipocytes , macrophages , endothelial and some epithelial cells , and exocrine and endocrine cells . By EM , subunit c was localized to all curvilinear type storage bodies , but to nowhere else within the cell . It was not present over fingerprint profiles , the characteristic storage pattern of neurons within the JB gut , possibly due to steric factors . preliminary studies in the mnd mouse showed subunit …

The CLN3 gene is a novel molecular target for cancer drug discovery. (2002 Feb)
The CLN3 gene is a novel molecular target for cancer drug discovery . juvenile batten disease is a neurodegenerative disease caused by accelerated apoptotic death of photoreceptors and neurons attributable to defects in the CLN3 gene . CLN3 is antiapoptotic when overexpressed in NT2 neuronal precursor cells . CLN3 negatively modulates endogenous ceramide levels in NT2 cells and acts upstream of ceramide generation . because defects in regulation of apoptosis are involved in the development of cancer , we evaluated the expression of CLN3 on both mRNA and protein levels in a variety of cancer cell lines and solid colon cancer tissue . We also observed the effect of the blocking of CLN3 protein expression on cancer cell growth , survival , ceramide production , and apoptosis by using an adenovirus bearing antisense CLN3 construct . We show that CLN3 mRNA and protein are overexpressed in glioblastoma ( U 373G and T98g ) , neuroblastoma ( IMR 32 and SK N MC ) , prostate ( du145 , PC 3 , and lncap ) , ovarian ( SK OV 3 , sw626 , and PA 1 ) , breast ( BT 20 , BT 549 , and BT 474 ) , and colon ( sw1116 , sw480 , and HCT 116 ) cancer cell lines but not in pancreatic ( capan and As PC 1 ) or lung ( A 549 and NCI H520 ) cancer cell lines . CLN3 is also up regulated in mouse melanoma and breast carcinoma …

Phenotypic reversal of the btn1 defects in yeast by chloroquine : a yeast model for batten disease. (1999 Oct)
phenotypic reversal of the btn1 defects in yeast by chloroquine : a yeast model for batten disease . BTN1 of saccharomyces cerevisiae encodes an ortholog of CLN3 , the human batten disease gene . We have reported previously that deletion of BTN1 , btn1 delta , resulted in a pH dependent resistance to D ( ) threo 2 amino 1 p nitrophenyl 1 , 3 propanediol ( ANP ) . This phenotype was caused by btn1 delta strains having an elevated ability to acidify growth medium through an elevated activity of the plasma membrane H ( ) atpase , resulting from a decreased vacuolar pH during early growth . We have determined that growing btn1 delta strains in the presence of chloroquine reverses the resistance to ANP , decreases the rate of medium acidification , decreases the activity of plasma membrane H ( ) atpase , and elevates vacuolar pH . however , an additional effect of this phenotypic reversal is that activity of plasma membrane H ( ) atpase is decreased further and vacuolar pH is increased further as btn1 delta strains continue to grow . This phenotypic reversal of btn1 delta can be considered for developing a therapy for batten disease .

Genetic analysis of batten disease. (1993 Nov)
genetic analysis of batten disease . batten disease , or neuronal ceroid lipofuscinosis ( CLN ) comprises a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurones . The three main childhood varieties infantile ( CLN1 ) , late infantile ( CLN2 ) and juvenile ( CLN3 ) manifest autosomal recessive inheritance . The basic biochemical defect remains unknown . The strategy of positional cloning is being pursued to elucidate the molecular basis of batten disease . The infantile disease locus ( CLN1 ) has been mapped by linkage analysis to human chromosome 1p32 , and the juvenile disease locus ( CLN3 ) to human chromosome 16p12 . In each case marker loci in strong linkage disequilibrium with the disease loci have been identified . locus heterogeneity between classical late infantile CLN ( CLN2 ) and both CLN1 and CLN3 has been demonstrated . Work is in progress to clone CLN1 and CLN3 and to map CLN2 . identification of linked markers has provided a new approach to prenatal diagnosis . The methodology exists for positional cloning of these genes and elucidation of the molecular genetic basis of the ceroid lipofuscinoses .

Diagnosis of neuronal ceroid lipofuscinosis ( batten disease ) by electron microscopy in peripheral blood specimens. (2006 Nov)
diagnosis of neuronal ceroid lipofuscinosis ( batten disease ) by electron microscopy in peripheral blood specimens . neuronal ceroid lipopofuscinosis ( batten disease , NCL ) represents a group of common childhood neurodegenerative diseases with a shared feature of deposition of abnormal metabolic products in neurons and other tissues , including peripheral blood lymphocytes . In most forms of NCL no specific enzyme defect is known and the diagnosis relies primarily on ultrastructural identification of characteristic membrane bound inclusions containing the abnormal metabolic product . All buffy coat specimens examined during a 7 year period ( 1997 2004 ) for the exclusion or confirmation of the diagnosis NCL were reviewed . From a total of 265 samples , 9 were inadequate and NCL was diagnosed in 56 . Five showed granular osmophilic deposits of infantile batten disease ( NCL1 ) , 10 showed curvilinear profiles of classical late infantile batten disease ( NCL2 ) , and 17 showed vacuolated lymphocytes with fingerprint profiles , indicating classical juvenile batten disease ( NCL3 ) . 24 samples ( 43 ) demonstrated compact electron dense deposits with fingerprint profiles in the absence of vacuolated lymphocytes , indicative of variant forms NCL . ultrastructual examination of peripheral blood allows reliable and specific diagnosis of subtypes of batten disease , including variants , and is a useful , minimally invasive test for the diagnosis of NCL in childhood .

Batten disease : new research findings on the biochemical defect. (1983 Feb)
batten disease : new research findings on the biochemical defect .

Mapping of the phenol sulfotransferase gene ( STP ) to human chromosome 16p12. (1994 Feb)
mapping of the phenol sulfotransferase gene ( STP ) to human chromosome 16p12 . 1 p11 . 2 and to mouse chromosome 7 . We have recently cloned a cDNA encoding the human phenol preferring phenol sulfotransferase ( P PST ) enzyme . An oligonucleotide primer pair based on the human STP ( representing sulfotransferase , phenol preferring ) cDNA sequence was synthesized and was employed in polymerase chain reaction ( PCR ) amplification of human genomic DNA to identify a 525 bp DNA fragment . The DNA sequence of this portion of the STP gene , near the 5 end of the coding region , was determined . The amplified genomic fragment contained two small introns of 104 and 89 bp . When DNA samples from a human hamster somatic cell hybrid panel were screened by PCR using these primers , only those hybrids that contained human chromosome 16 were positive for the 525 bp genomic fragment . To identify the specific region on chromosome 16 that contained the STP gene , PCR amplification reactions were performed on a human mouse somatic cell hybrid panel containing defined portions of human chromosome 16 . The results indicated that STP is localized proximal to the gene for protein kinase C , beta 1 polypeptide ( prkcb1 ) , in the region from the distal portion of 16p11 . 2 to p12 . 1 . The human STP gene maps near the locus for batten disease ( CLN3 ) . furthermore , …

Morphological alterations in neocortical and cerebellar gabaergic neurons in a canine model of juvenile batten disease. (1995 Oct)
morphological alterations in neocortical and cerebellar gabaergic neurons in a canine model of juvenile batten disease . The pathogenesis of brain dysfunction in a canine model of juvenile batten disease was studied with techniques designed to determine sequential changes in mitochondrial morphology and cytochrome oxidase ( CO ) activity , and in neurons and synapses using gamma aminobutyric acid ( GABA ) as a neurotransmitter . histochemical and immunocytochemical methods were employed . mitochondrial alterations were found in a select population of nonpyramidal neurons in neocortex and claustrum , and in cerebellar basket cells . proportions of affected neurons at any one time remained constant over the disease course , with morphologically abnormal mitochondria first being recognized at age 6 months . enlarged mitochondria were readily identifiable at the light microscope ( LM ) level as large CO positive or mitochondrial antibody positive granular structures . colabelling with antibodies to GABA or to parvalbumin ( PV ) indicated that most of these cells were gabaergic . ultrastructurally , atypical mitochondria were characterized by globular enlargement , intramitochondrial membranous inclusions , and disorganized internal structure . CO activity in all other cell somata and in neuropil was diminished compared with normal , age matched tissue . glutamic acid decarboxylase ( GAD ) , PV , and GABA studies demonstrated loss of gabaergic neurons and synapses in cortex and cerebellum of affected dogs . these results indicate that abnormal mitochondria are present in neurons in batten disease , and suggest that suboptimal …

Batten disease ( spielmeyer Vogt disease , juvenile onset neuronal ceroid lipofuscinosis ) gene ( CLN3 ) maps to human … (1991 Jan)
batten disease ( spielmeyer Vogt disease , juvenile onset neuronal ceroid lipofuscinosis ) gene ( CLN3 ) maps to human chromosome 16 . The ceroid lipofuscinoses are a group of inherited neurodegenerative disorders characterized by the accumulation of autofluorescent lipopigment in neurons and other cell types . The underlying biochemical defect is unknown . batten disease ( spielmeyer Vogt disease , juvenile onset neuronal ceroid lipofuscinosis ) displays autosomal recessive inheritance . genetic linkage studies were undertaken to determine the chromosomal location of the batten disease mutation ( CLN3 ) . following identification of linkage to the haptoglobin locus , linkage analysis has been carried out in 42 families by using DNA markers for loci on the long arm of human chromosome 16 . The maximal lod score between batten disease and the locus d16s148 calculated for combined sexes is 6 . 05 at a recombination fraction theta 0 . 00 . multilocus analysis using five loci indicated the most likely order to be HP d16s151 d16s150 CLN3 d16s148 d16s147 . The maximal location score for CLN3 was 48 ( equivalent to a lod score of 10 . 4 ) in that interval within this fixed marker map .

Infantile neuronal ceroid lipofuscinosis is not an allelic form of batten disease : exclusion of chromosome 16 region with linkage … (1991 Jan)
infantile neuronal ceroid lipofuscinosis is not an allelic form of batten disease : exclusion of chromosome 16 region with linkage analyses . infantile neuronal ceroid lipofuscinosis ( CLN1 ) is the form of neuronal ceroid lipofuscinoses ( NCL ) with the earliest onset of symptoms . The locus of the most common form of these disorders , juvenile NCL ( CLN3 ) , has been mapped to chromosome 16 . We report here linkage data of the same region in finnish CLN1 families . Our results indicate that CLN1 is not allelic with CLN3 but represents a different locus , which is not located within about 70 cM in chromosome 16 .

Fine genetic mapping of the batten disease locus ( CLN3 ) by haplotype analysis and demonstration of allelic association with … (1993 Jul)
Fine genetic mapping of the batten disease locus ( CLN3 ) by haplotype analysis and demonstration of allelic association with chromosome 16p microsatellite loci . batten disease , juvenile onset neuronal ceroid lipofuscinosis , is an autosomal recessive neurodegenerative disorder characterized by accumulation of autofluorescent lipopigment in neurons and other cell types . The disease locus ( CLN3 ) has previously been assigned to chromosome 16p . The genetic localization of CLN3 has been refined by analyzing 70 families using a high resolution map of 15 marker loci encompassing the CLN3 region on 16p . crossovers in three maternal meioses allowed localization of CLN3 to the interval between d16s297 and d16s57 . within that interval alleles at three highly polymorphic dinucleotide repeat loci ( d16s288 , d16s298 , d16s299 ) were found to be in strong linkage disequilibrium with CLN3 . analysis of haplotypes suggests that a majority of CLN3 chromosomes have arisen from a single founder mutation .

Structure of the CLN3 gene and predicted structure , location and function of CLN3 protein. (1997 Aug)
structure of the CLN3 gene and predicted structure , location and function of CLN3 protein . The genomic sequence of the human CLN3 gene , which is defective in juvenile onset neuronal ceroid lipofuscinosis ( batten disease ) is being delineated using a variety of methods . A saccharomyces cerevisiae gene , YHC3 ( for yeast homologue to human CLN3 ) , which is highly similar to the human disease gene , has been identified by computer aided homology searching . topology predictions indicate the CLN3 protein contains six transmembrane segments . Most similarity between the human and yeast proteins lies either in the transmembrane segments or along one face of the predicted protein structure .

Strategy for mutation detection in CLN3 : characterisation of two finnish mutations. (1997 Aug)
strategy for mutation detection in CLN3 : characterisation of two finnish mutations . A strategy for detection of mutations in CLN3 , the gene for batten disease or juvenile onset neuronal ceroid lipofuscinosis , has been devised using a technique which detects conformation polymorphisms and direct sequencing of genomic DNA fragments . We define two mutations found uniquely in finnish patients , one a large deletion ( 2 . 8 kb ) , the other a point mutation affecting the 5 splice donor site of an intron .

Rate of accumulation of luxol Fast Blue staining material and mitochondrial ATP synthase subunit 9 in motor neuron degeneration mice. (1999 Jan)
Rate of accumulation of luxol Fast Blue staining material and mitochondrial ATP synthase subunit 9 in motor neuron degeneration mice . The rate of accumulation of luxol Fast Blue staining material in the hippocampus of motor neuron degeneration ( mnd / mnd ) mice , a model of batten disease , was quantitated . stained material increased linearly up to 8 months of age . A quantitative immunoassay was used to measure levels of mitochondrial ATP synthase subunit 9 in brain and liver of mnd / mnd mice . levels of subunit 9 increased progressively throughout the lifespan of mnd / mnd mice reaching levels approximately 5 fold higher than in control animals . The rate of accumulation of subunit 9 is not consistent with any simple complete or partial degradation defect that is constant throughout the animal s life . Two more complicated models are discussed which are consistent with the observed accumulation rate of subunit 9 .