WDR45 contains 12 exons, with the first 2 non-coding. Pathogenic variants have been documented in coding exons 3-12 and include all categories of variants (missense, nonsense, splicing, and intragenic deletions / insertions). The majority of reported variants are predicted to cause a loss of function. Nearly all pathogenic variants in WDR45 are de novo.
Diagnostic testing approaches may include single-gene testing, gene-targeted testing with specialized panels, or exome or genome sequencing depending on the phenotype. Since findings in young children with BPAN (such as developmental delay or seizures) are common, many are diagnosed after comprehensive sequencing or panel testing, such as with a seizure panel or autism panel.
WDR45 encodes the WD repeat domain phosphoinositide-interacting protein (WIPI4). WIPI4 is a member of a larger family of proteins with repeating units that form a seven-bladed, beta-propeller structure. WIPI4 associates with known autophagy proteins but its role in the autophagic process is not yet understood.
WDR45