Functional mRNA analysis reveals aberrant splicing caused by novel intronic mutation in WDR45 in NBIA patient

Am J Med Genet A. 2018 May;176(5):1049-1054. doi: 10.1002/ajmg.a.38656.


WDR45 gene-associated neurodegeneration with brain iron accumulation (NBIA), referred to as beta-propeller protein-associated neurodegeneration (BPAN), is a rare disorder that presents with a very nonspecific clinical phenotype in children constituting global developmental delay. This case report illustrates the power of a combination of trio exome sequencing, in silico splicing analysis, and mRNA analysis to provide sufficient evidence for pathogenicity of a relatively intronic variant in WDR45, and in so doing, find a genetic diagnosis for a 6-year-old patient with developmental delay and seizures, a diagnosis which may otherwise have only been found once the characteristic MRI patterns of the disease became more obvious in young adulthood.

Keywords: MRI-brain; WDR45; cultured fibroblasts; in silico analysis; intronic; iron accumulation; mRNA analysis; mutation; splicing.

Publication types

  • Case Reports

MeSH terms

  • Alleles
  • Brain / pathology
  • Carrier Proteins / genetics*
  • Child
  • Comparative Genomic Hybridization
  • Exons
  • Female
  • Gene Expression Profiling
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Introns*
  • Magnetic Resonance Imaging / methods
  • Mutation*
  • Neuroaxonal Dystrophies / diagnosis
  • Neuroaxonal Dystrophies / genetics*
  • Phenotype
  • RNA Splicing*
  • RNA, Messenger*
  • Sequence Analysis, DNA
  • Transcriptome


  • Carrier Proteins
  • RNA, Messenger
  • WDR45 protein, human