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

Tremor Other Hyperkinet Mov (N Y). 2017 Aug 8;7:465. doi: 10.7916/D8251WB0. eCollection 2017.

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.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Carrier Proteins / genetics*
  • Female
  • Heterozygote*
  • Humans
  • Iron Metabolism Disorders / diagnostic imaging
  • Iron Metabolism Disorders / drug therapy
  • Iron Metabolism Disorders / genetics*
  • Neuroaxonal Dystrophies / diagnostic imaging
  • Neuroaxonal Dystrophies / drug therapy
  • Neuroaxonal Dystrophies / genetics*
  • Phenotype
  • Sequence Deletion*

Substances

  • Carrier Proteins
  • WDR45 protein, human

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)