Dataset Information

Chorea-acanthocytosis genotype in the original critchley kentucky neuroacanthocytosis kindred.

ABSTRACT:

Objective

To determine the molecular nature of the neurological disease in the seminal family reported by Critchley et al in the 1960s, characterized by a hyperkinetic movement disorder and the appearance of acanthocytosis on peripheral blood smear. The eponym Levine-Critchley syndrome, subsequently termed neuroacanthocytosis, has been applied to symptomatically similar, but genetically distinct, disorders, resulting in clinical and diagnostic confusion.

Design

DNA analysis.

Setting

Molecular biology research laboratories.

Participants

First- and second-degree relatives of the original Critchley et al proband from Kentucky.

Main outcome measures

Mutations in the VPS13A gene.

Results

A mutation was identified in the VPS13A gene, responsible for autosomal recessive chorea-acanthocytosis. Haplotype reconstruction suggested that this mutation was homozygous in the proband.

Conclusion

These findings strongly support the diagnosis of chorea-acanthocytosis as the disorder described in the original report.

SUBMITTER: Velayos-Baeza A

PROVIDER: S-EPMC4615612 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature

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Publications

Chorea-acanthocytosis genotype in the original critchley kentucky neuroacanthocytosis kindred.

Velayos-Baeza Antonio A Holinski-Feder Elke E Neitzel Birgit B Bader Benedikt B Critchley Edmund M R EM Monaco Anthony P AP Danek Adrian A Walker Ruth H RH

Archives of neurology 20111001 10

<h4>Objective</h4>To determine the molecular nature of the neurological disease in the seminal family reported by Critchley et al in the 1960s, characterized by a hyperkinetic movement disorder and the appearance of acanthocytosis on peripheral blood smear. The eponym Levine-Critchley syndrome, subsequently termed neuroacanthocytosis, has been applied to symptomatically similar, but genetically distinct, disorders, resulting in clinical and diagnostic confusion.<h4>Design</h4>DNA analysis.<h4>Se ...[more]

PMID: 21987550

Similar Datasets

Project description:BackgroundVacuolar protein sorting 13 homolog A (VPS13A) disease, historically known as chorea-acanthocytosis, is a rare neurodegenerative disorder caused by biallelic mutations in VPS13A, usually resulting in reduced or absent levels of its protein product, VPS13A. VPS13A localizes to contact sites between subcellular organelles, consistent with its recently identified role in lipid transfer between membranes. Mutations are associated with neuronal loss in the striatum, most prominently in the caudate nucleus, and associated marked astrogliosis. There are no other known disease-specific cellular changes (eg, protein aggregation), but autopsy reports to date have been limited, often lacking genetic or biochemical diagnostic confirmation.ObjectiveThe goal of this study was to characterize neuropathological findings in the brains of seven patients with VPS13A disease (chorea-acanthocytosis).MethodsIn this study, we collected brain tissues and clinical data from seven cases of VPS13A for neuropathological analysis. The clinical diagnosis was confirmed by the presence of VPS13A mutations and/or immunoblot showing the loss or reduction of VPS13A protein. Tissues underwent routine, special, and immunohistochemical staining focused on neurodegeneration. Electron microscopy was performed in one case.ResultsGross examination showed severe striatal atrophy. Microscopically, there was neuronal loss and astrogliosis in affected regions. Luxol fast blue staining showed variable lipid accumulation with diverse morphology, which was further characterized by electron microscopy. In some cases, rare degenerating p62- and ubiquitin-positive cells were present in affected regions. Calcifications were present in four cases, being extensive in one.ConclusionsWe present the largest autopsy series of biochemically and genetically confirmed VPS13A disease and identify novel histopathological findings implicating abnormal lipid accumulation. © 2023 International Parkinson and Movement Disorder Society.

Dataset Information

Chorea-acanthocytosis genotype in the original critchley kentucky neuroacanthocytosis kindred.

Objective

Design

Setting

Participants

Main outcome measures

Results

Conclusion

Publications

Chorea-acanthocytosis genotype in the original critchley kentucky neuroacanthocytosis kindred.

Similar Datasets

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