Mutations in Extracellular Matrix Genes NID1 and LAMC1 Cause Autosomal Dominant Dandy–Walker Malformation and Occipital Cephaloceles

We performed whole-exome sequencing of a family with autosomal dominant Dandy-Walker malfor- mation and occipital cephaloceles and detected a mutation in the extracellular matrix (ECM) protein-encoding gene NID1. In a second family, protein interaction network analysis identified a mutation in LAMC1, which encodes a NID1-binding partner. Structural modeling of the NID1- LAMC1 complex demonstrated that each mutation dis- rupts the interaction. These findings implicate the ECM in the pathogenesis of Dandy-Walker spectrum disorders.