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Case Reports
. 2017 Aug 8:7:465.
doi: 10.7916/D8251WB0. eCollection 2017.

A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion of WDR45

Andreas Hermann  1 , Hagen H Kitzler  2 , Tobias Pollack  3 , Saskia Biskup  4 , Stefanie Krüger  4 , Claudia Funke  4 , Caterina Terrile  5 , Tobias B Haack  5   6
Affiliations
Case Reports

A Case of Beta-propeller Protein-associated Neurodegeneration due to a Heterozygous Deletion of WDR45

Andreas Hermann et al. Tremor Other Hyperkinet Mov (N Y). .

Abstract

Background: Static encephalopathy of childhood with neurodegeneration in adulthood is a phenotypically distinctive, X-linked dominant subtype of neurodegeneration with brain iron accumulation (NBIA). WDR45 mutations were recently identified as causal. WDR45 encodes a beta-propeller scaffold protein with a putative role in autophagy, and the disease has been renamed beta-propeller protein-associated neurodegeneration (BPAN).

Case report: Here we describe a female patient suffering from a classical BPAN phenotype due to a novel heterozygous deletion of WDR45. 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 WDR45 coding regions was undertaken, and this showed a reduction of the gene dosage by 50% compared with controls.

Discussion: An extended search for deletions should be performed in apparently WDR45-negative cases presenting with features of NBIA and should also be considered in young patients with predominant intellectual disabilities and hypertonia/parkinsonism/dystonia.

Keywords: BPAN; NBIA; SENDA; Static encephalopathy of childhood with neurodegeneration in adulthood; WDR45; beta-propeller protein-associated neurodegeneration.

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Conflict of interest statement

Funding: None. Conflict of Interest: The authors report no conflict of interest. Ethics Statement: This study was reviewed by the authors’ institutional ethics committee and was considered exempted from further review.

Figures

Figure 1
Figure 1. Neuroimaging and Genetics of Referred Patient. (A–F) Patient brain magnetic resonance imaging panel displaying T2 weighted (A,D) and T1 weighted scans of consecutive axial slices at mesencephalic and basal ganglia level. Beta-propeller protein-associated neurodegeneration (BPAN) typical signal changes were found as symmetric cerebral peduncle including substantia nigra T2 hypointensity (A,F;*) combined with T1 hyperintensity (B) with a located circumscribed hypointense band in there (B and enlarged section C;<) as described to be a nearly pathognomonic magnetic resonance imaging feature of BPAN. In contrast, symmetric T2 hypointensity of the globus pallidus (D,F;→) was not accompanied by T1 signal changes (E). Global cerebral atrophy and caudate nucleus atrophy were observed. (G) Quantitative polymerase chain reaction of the WDR45 coding regions of the index patient and her parents showing a reduction of the gene dosage to approximately 50% of controls suggestive of a heterozygous deletion of the entire WDR45 gene.
See this image and copyright information in PMC

References

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