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

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.