Chorea-acanthocytosis genotype in the original critchley kentucky neuroacanthocytosis kindred
Antonio Velayos-Baeza1, Elke Holinski-Feder, Birgit Neitzel
1The Wellcome Trust Centre for Human Genetics, Oxford, England.
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.
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