Japanese WDR45 de novo mutation diagnosed by exome analysis: A case report

A 40-year-old Japanese woman presented with slowly progressing parkinsonism in adulthood. She had a history of epilepsy with intellectual disability in childhood. In a head magnetic resonance scan, T2-weighted imaging showed low signal intensity areas in the globus pallidus and the substantia nigra; T1-weighted imaging showed a halo in the nigra. Because the patient's symptoms and history were similar to those of patients with neurodegeneration with brain iron accumulation, we ran an exome analysis to investigate neurodegeneration with brain iron accumulation-associated genes. We identified a c.700 C>T (p.Arg 234*) mutation in exon 9 of the WDR45 gene, which had not been reported in Japanese patients with beta-propeller protein-associated neurodegeneration (a neurodegeneration with brain iron accumulation subtype). Sanger sequencing confirmed a heterozygous mutation in this patient that was absent in both her parents, so it was judged to be a de novo nonsense mutation.