Cerebrospinal fluid and serum glycosphingolipid biomarkers in canine globoid cell leukodystrophy (Krabbe Disease)

This study identified several biomarkers which may be useful in the development of therapeutics for GLD.
Source: Molecular and Cellular Neuroscience - Category: Neuroscience Source Type: research

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AbstractBiallelic variants inPOLR3A cause 4H leukodystrophy, characterized by hypomyelination in combination with cerebellar and pyramidal signs and variable non-neurological manifestations. Basal ganglia are spared in 4H leukodystrophy, and dystonia is not prominent. Three patients with variants inPOLR3A, an atypical presentation with dystonia, and MR involvement of putamen and caudate nucleus (striatum) and red nucleus have previously been reported. Genetic, clinical findings and 18 MRI scans from nine patients with homozygous or compound heterozygousPOLR3A variants and predominant striatal changes were retrospectively r...
Source: Neurogenetics - Category: Genetics & Stem Cells Source Type: research
This study was a retrospective analysis of data from 834 patients with molecularly confirmed ARCAs, including 57 NPC cases (RADIAL cohort). We aimed to compare the algorithm performance of RADIAL (Top 1 and Top 3) with that of four SIs (Original, Refined, 2/3 and 2/7) in discriminating NPC cases and non-NPC cases. We also identified ARCAs closely related to NPC as those with low specificity to detect non-NPC cases and described differential and overlapping features with NPC. Overall, excellent sensitivity and specificity (> 0.90) were achieved with both RADIAL and SI tools for NPC cases. The highest sensitivity w...
Source: Cerebellum - Category: Neuroscience Authors: Tags: Cerebellum Source Type: research
This study was a retrospective analysis of data from 834 patients with molecularly confirmed ARCAs, including 57 NPC cases (RADIAL cohort). We aimed to compare the algorithm performance of RADIAL (Top 1 and Top 3) with that of four SIs (Original, Refined, 2/3 and 2/7) in discriminating NPC cases and non-NPC cases. We also identified ARCAs closely related to NPC as those with low specificity to detect non-NPC cases and described differential and overlapping features with NPC. Overall, excellent sensitivity and specificity (>  0.90) were achieved with both RADIAL and SI tools for NPC cases. The highest sensitivity ...
Source: The Cerebellum - Category: Neurology Source Type: research
Biallelic variants in POLR3A encoding the largest subunit of RNA polymerase III cause POLR3-related (or 4H) leukodystrophy characterized by neurologic dysfunction, abnormal dentition, endocrine abnormalities and ocular abnormality. Recently, whole-exome sequencing enabled the discovery of POLR3A variants in cases lacking diffuse hypomyelination, the principal MRI phenotype of POLR3-related leukodystrophy. Homozygous c.1771-6C  > G variants in POLR3A were recently suggested to cause striatal and red nucleus involvement without white matter involvement.
Source: Brain and Development - Category: Neurology Authors: Tags: Case Report Source Type: research
Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is a rare form of infantile-onset leukodystrophy. The disorder is caused primarily by mutations of MLC1 that leads to a series of phenotypic outcom...
Source: Molecular Brain - Category: Neuroscience Authors: Tags: Research Source Type: research
AbstractPhelan-McDermid syndrome (PMS) is caused by haploinsufficiency of theSHANK3 gene on chromosome 22q13.33 and is characterized by intellectual disability, hypotonia, severe speech impairments, and autism spectrum disorder. Emerging evidence indicates that there are changes over time in the phenotype observed in individuals with PMS, including severe neuropsychiatric symptoms and loss of skills occurring in adolescence and adulthood. To gain further insight into these phenomena and to better understand the long-term course of the disorder, we conducted a systematic literature review and identified 56 PMS cases showing...
Source: Molecular Autism - Category: Molecular Biology Source Type: research
In this study, to determine the novel alanyl-tRNA synthetase 2 mutation implicated in white matter disease, several families with an autosomal recessive inheritance pattern of white matter disease were analyzed by whole-exome sequencing. Variants were prioritized according to their rarity and pathogenic variants in genes already known to be associated with leukodystrophies and were confirmed by Sanger sequencing using standard protocols. We identified 5 rare variants (c.452T>C chr6:44279256 p.M151T, c.1871G>A chr6:44272054 p.W624X, c.802A>G chr6:44278128 p.M268V, c.1703-1704del chr6:-44272430-44272431 p.Q568fs, an...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
FA2H encodes fatty acid 2-hydroxylase, which plays a significant role in maintaining the neuronal myelin sheath. Previous reports have revealed that a FA2H mutation leads to spastic paraplegia, leukodystrophy, and neurodegeneration with brain iron accumulation, collectively referred to as fatty acid hydroxylase-associated neurodegeneration (FAHN). The disease severity of FAHN varies among individual patients and may be explained by the enzyme activity of FA2H mutant proteins. Here we report a 10-year-old Japanese boy with FAHN having novel heterozygous mutations in FA2H.
Source: Brain and Development - Category: Neurology Authors: Tags: Case Report Source Type: research
ConclusionThe syndromic nature and selective vulnerability of white matter tracts in these disorders suggests there may be a shared mechanism of mitochondrial dysfunction to target for study. There is evidence that the clinical variability and white matter tract specificity of each mt-aaRS leukodystrophy depend on both canonical and non-canonical effects of the mutations on the process of mitochondrial translation. Furthermore, different sensitivities to the mt-aaRS mutations have been observed based on cell type. Most mutations result in at least partial retention of mt-aaRS enzyme function with varied effects on the mito...
Source: Journal of Neurodevelopmental Disorders - Category: Neurology Source Type: research
Publication date: Available online 14 December 2019Source: Journal of Pediatric Surgery Case ReportsAuthor(s): Eduje Thomas, Tommaso Gargano, Michele Libri, Giovanni Ruggeri, Nunzio Salfi, Mario Lima, Elisa Mazzoni
Source: Journal of Pediatric Surgery Case Reports - Category: Surgery Source Type: research
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