<b>DIAPH1</b><b> Regulates the Wnt/β-catenin Pathway Resulting in Microcephaly and Visual Impairment</b>

This study was designed to elucidate the pathogenesis of microcephaly syndrome caused by the mutation in double allele mutation of DIAPH1. We conducted high throughput whole exome sequencing on patient's peripheral blood. Due to Zebrafish lacking human DIAPH1 homolog, we used it to establish the microcephaly model by introducing the human DIAPH1 gene. Exome sequencing found compound heterozygous DIAPH1 mutations causing clinical symptoms. Mutated DIAPH1 zebrafish displayed abnormal eye shape, short body length, axis defects, aberrant neuronal motor axon growth, and reduced behavioral activities. WNT8A, WNT9A, LRP5, and LRP6 genes were upregulated, while AXIN1, AXIN2, and Β-CATENIN were downregulated, suggesting Wnt/β-catenin pathway involvement. DIAPH1 mutation (c.1051C&gt;T, p.R351X,922; c.609delA, p.E203E fs*19) might causes microcephaly and visual impairment via activated Wnt/β-catenin pathway.