Project description:UnlabelledThe case of a 66 year-old female - the oldest known living patient with Niemann-Pick disease type C (NP-C) who remains free of any neurological or psychiatric manifestations 18 years after presentation - is presented. An incidental finding of massive splenomegaly was detected during a routine pelvic ultrasound. The pathology report after splenectomy showed the presence of lipid-laden macrophages. Fibroblasts cultured in LDL-enriched medium revealed abnormal filipin staining consistent with cholesterol-filled vesicles and the rate of cholesterol esterification in response to stimulation of LDL-cholesterol uptake was significantly depressed at 6% of that seen in cells from normal controls, but at a level similar to that observed in an NP-C positive control. Molecular genetic testing later revealed a compound heterozygous mutant NP-C genotype comprising two previously described disease-causing mutations in the NPC1 gene, one in exon 8 (c.1133T>C [V378A]) and one in exon 13 (c.1990G>A [V664M]). These findings confirmed the diagnosis of NP-C. Only three patients with this disorder aged > 53 years have previously been reported, all of whom presented with neurological or neuropsychiatric manifestations. Our patient is the first reported NP-C patient, now in her seventh decade of life, who has to date only manifested splenomegaly. This case highlights the extreme clinical variability of NP-C, and the need to consider this disease in the differential diagnosis of organomegaly, even in the absence of neurological, psychiatric and related clinical signs.SynopsisAn elderly female patient with confirmed NP-C and isolated splenomegaly has remained asymptomatic for neurological, cognitive, psychiatric or ophthalmologic abnormailities into her seventh decade of life.

| S-EPMC4750631 | biostudies-literature

Niemann-Pick type C fibroblast analysis

Project description:Primary skin fibroblasts from four Niemann-Pick type C patients homozygous for the I1061T mutation and four control individuals were cultured under identical conditions in DMEM containing 10% fetal bovine serum. Cells were harvested at 50-70% confluency. mRNA was isolated with the FastTrack 2.0 mRNA isolation kit according to the manufacturer's instructions (Invitrogen, Carlsbad, CA). A reference RNA comprised of 10 cell lines was used as the control for each hybridized sample (Stratagene, La Jolla, CA). Both sample and reference RNAs were amplified using the MessageAmp II aRNA amplification kit (Ambion, Austin, TX). Set of arrays that are part of repeated experiments Keywords: Biological Replicate

2007-08-15 | GSE8770 | GEO

Niemann-Pick type C fibroblast analysis

2007-08-15 | E-GEOD-8770 | biostudies-arrayexpress

Modeling Brain Pathology of Niemann-Pick Disease Type C Using Patient-Derived Neurons.

Project description:BackgroundNiemann-Pick disease type C (NPC) is a rare autosomal-recessive lysosomal storage disease that is also associated with progressive neurodegeneration. NPC shares many pathological features with Alzheimer's disease, including neurofibrillary tangles, axonal spheroids, β-amyloid deposition, and dystrophic neurites. Here, we examined if these pathological features could be detected in induced pluripotent stem cell (iPSC)-derived neurons from NPC patients.MethodsBrain tissues from 8 NPC patients and 5 controls were analyzed for histopathological and biochemical markers of pathology. To model disease in culture, iPSCs from NPC patients and controls were differentiated into cortical neurons.ResultsWe found hyperphosphorylated tau, altered processing of amyloid precursor protein, and increased Aβ42 in NPC postmortem brains and in iPSC-derived cortical neurons from NPC patients.ConclusionOur findings demonstrated that the main pathogenic phenotypes typically found in NPC brains were also observed in patient-derived neurons, providing a useful model for further mechanistic and therapeutic studies of NPC. © 2021 International Parkinson and Movement Disorder Society.

| S-EPMC8422975 | biostudies-literature

Gelastic Cataplexy in Niemann Pick Type C.

Project description: Not available

| S-EPMC6660230 | biostudies-literature