An unusual presentation of late-onset Alexander's disease with slow orthostatic tremor and a novel GFAP variant.

We report a case of AOAD, with onset in the eighth decade, presenting with slow variant orthostatic tremor, which has not been previously described. Genetic analysis revealed a GFAP variant (c.1158C>A) that has not been previously reported. Our case serves to expand the diagnostic spectrum of AOAD both clinically and genetically. PMID: 30755139 [PubMed - as supplied by publisher]
Source: Neurocase - Category: Neurology Authors: Tags: Neurocase Source Type: research

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To describe the genetic variants in the ARSA gene in Sri Lankan patients with metachromatic leukodystrophy (MLD). As the variant profile of MLD in the Sri Lankan population is currently unknown.
Source: BMC Research Notes - Category: Research Authors: Tags: Research note Source Type: research
Metachromatic leukodystrophy (MLD) is an autosomal recessively inherited metabolic disease characterized by deficient activity of the lysosomal enzyme arylsulfatase A. Its deficiency results in accumulation of...
Source: Orphanet Journal of Rare Diseases - Category: Internal Medicine Authors: Tags: Review Source Type: research
Publication date: Available online 22 October 2019Source: Stem Cell ResearchAuthor(s): S Masneri, G Lanzi, RM Ferraro, C Barisani, G Piovani, G Savio, M Cattalini, J Galli, C Cereda, M Muzi-Falconi, S Orcesi, E Fazzi, S GilianiAbstractAicardi-Goutières syndrome (AGS) is an early-onset monogenic encephalopathy characterized by intracranial calcification, leukodystrophy and cerebrospinal fluid lymphocytosis. To date, seven genes have been related to AGS. Among these, IFIH1 encodes for MDA5, a cytosolic double-stranded RNA receptor, and is responsible for AGS type7. We generated three isogenic iPSC clones, using a Send...
Source: Stem Cell Research - Category: Stem Cells Source Type: research
Abstract Zellweger spectrum disorders (ZSD) constitute a group of rare autosomal recessive disorders characterized by a defect in peroxisome biogenesis due to mutations in one of 13 PEX genes. The broad clinical heterogeneity especially in late-onset presenting patients and a mild phenotype complicates and delays the diagnostic process. Here, we report a case of mild ZSD, due to novel PEX1 variants. The patient presented with an early hearing loss, bilateral cataracts, and leukodystrophy on magnetic resonance (MR) images. Normal results of serum very-long-chain fatty acids (VLCFA) and phytanic acid were found. Mol...
Source: J Appl Genet - Category: Genetics & Stem Cells Authors: Tags: J Appl Genet Source Type: research
Contributors : No émie Hamilton ; Jutta GaertnerSeries Type : Expression profiling by arrayOrganism : Danio rerioRNASET2-deficient leukoencephalophathy is a severe leukodystrophy affecting children with psychomotor impairements in their forst year of life. We generated the first zebrafish model for a human leukodystrophy by targetting the ortholog rnaset2 gene using mutagenesis. This zebrafish mutant recapitulated the human clinical manisfestations and developed white matter defects detectable by MRI. Additionally, this zebrafish mutant identified this disease as a lysosomal storage disorders, with RNA accumulating ...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by array Danio rerio Source Type: research
Authors: Jorge MS, Bugiani M Abstract Leukodystrophies are genetically determined disorders affecting the white matter of the central nervous system. The combination of MRI pattern recognition and next-generation sequencing for the definition of novel disease entities has recently demonstrated that many leukodystrophies are due to the primary involvement and/or mutations in genes selectively expressed by cell types other than the oligodendrocytes, the myelin-forming cells in the brain. This has led to a new definition of leukodystrophies as genetic white matter disorders resulting from the involvement of any white ...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
Authors: Verkhratsky A, Ho MS, Vardjan N, Zorec R, Parpura V Abstract Astroglial cells are involved in most if not in all pathologies of the brain. These cells can change the morpho-functional properties in response to pathology or innate changes of these cells can lead to pathologies. Overall pathological changes in astroglia are complex and diverse and often vary with different disease stages. We classify astrogliopathologies into reactive astrogliosis, astrodegeneration with astroglial atrophy and loss of function, and pathological remodelling of astrocytes. Such changes can occur in neurological, neurodevelopme...
Source: Advances in Experimental Medicine and Biology - Category: Research Tags: Adv Exp Med Biol Source Type: research
We report a hereditary leukodystrophy in Standard Schnauzer puppies. Clinical signs occurred shortly after birth or started at an age of under 4 weeks and included apathy, dysphoric vocalization, hypermetric ataxia, intension tremor, head tilt, circling, proprioceptive deficits, seizures and ventr al strabismus consistent with a diffuse intracranial lesion. Magnetic resonance imaging revealed a diffuse white matter disease without mass effect. Macroscopically, the cerebral white matter showed a gelatinous texture in thecentrum semiovale. A mild hydrocephalus internus was noted. Histopathologically, a severe multifocal redu...
Source: PLoS Genetics - Category: Genetics & Stem Cells Authors: Source Type: research
Mechanically activated (MA) ion channels convert physical forces into electrical signals. Despite the importance of this function, the involvement of mechanosensitive ion channels in human disease is poorly understood. Here we report heterozygous missense mutations in the gene encoding the MA ion channel TMEM63A that result in an infantile disorder resembling a hypomyelinating leukodystrophy. Four unrelated individuals presented with congenital nystagmus, motor delay, and deficient myelination on serial scans in infancy, prompting the diagnosis of Pelizaeus-Merzbacher (like) disease.
Source: The American Journal of Human Genetics - Category: Genetics & Stem Cells Authors: Tags: Report Source Type: research
Abstract Pelizaeus-Merzbacher disease (PMD) is an X-linked leukodystrophy caused by mutations in Proteolipid Protein 1 (PLP1), encoding a major myelin protein, resulting in profound developmental delay and early lethality. Previous work showed involvement of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress pathways, but poor PLP1 genotype-phenotype associations suggest additional pathogenetic mechanisms. Using induced pluripotent stem cell (iPSC) and gene-correction, we show that patient-derived oligodendrocytes can develop to the pre-myelinating stage, but subsequently undergo cell death. Mut...
Source: Cell Stem Cell - Category: Stem Cells Authors: Tags: Cell Stem Cell Source Type: research
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