A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion ofWDR45

Tremor and Other Hyperkinetic Movements
Andreas HermannTobias Haack

Abstract

Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA).WDR45mutations were recently identified as causal.WDR45encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN). Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion ofWDR45. An initial gene panel and Sanger sequencing approach failed to uncover the molecular defect. Based on the typical clinical and neuroimaging phenotype, quantitative polymerase chain reaction of theWDR45coding regions was undertaken, and this showed a reduction of the gene dosage by 50% compared with controls. An extended search for deletions should be performed in apparentlyWDR45-negative cases presenting with features of NBIA and should also be considered in young patients with predominant intellectual disabilities and hypertonia/parkinsonism/dystonia.

Citations

Nov 6, 2018·Brain Sciences·Edward BotsfordEllen E Buckley

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BETA
PCR

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