A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion of <em>WDR45</em>

• Main Authors: Andreas Hermann, Hagen H. Kitzler, Tobias Pollack, Saskia Biskup, Stefanie Krüger, Claudia Funke, Caterina Terille, Tobias B. Haack
• Format: Article
• Language: English
• Published: Ubiquity Press 2017-08-01
• Series: Tremor and Other Hyperkinetic Movements
• Online Access: https://tremorjournal.org/index.php/tremor/article/view/465

<p><strong>Background:</strong>&nbsp;Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA).&nbsp;<em>WDR45</em>&nbsp;mutations were recently identified as causal.&nbsp;<em>WDR45</em>&nbsp;encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN).</p><p><strong>Case Report:</strong>&nbsp;Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of&nbsp;<em>WDR45</em>. 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 the&nbsp;<em>WDR45</em>&nbsp;coding regions was undertaken, and this showed a reduction of the gene dosage by 50% compared with controls.</p><p><strong>Discussion:</strong>&nbsp;An extended search for deletions should be performed in apparently&nbsp;<em>WDR45-</em>negative cases presenting with features of NBIA and should also be considered in young patients with predominant intellectual disabilities and hypertonia/parkinsonism/dystonia.</p>