Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant Dandy-Walker malformation and occipital cephaloceles

Hum Mutat. 2013 Aug;34(8):1075-9. doi: 10.1002/humu.22351. Epub 2013 May 28.

Abstract

We performed whole-exome sequencing of a family with autosomal dominant Dandy-Walker malformation 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 disrupts the interaction. These findings implicate the ECM in the pathogenesis of Dandy-Walker spectrum disorders.

Keywords: Dandy-Walker; LAMC1; NID1; exome; extracellular matrix.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dandy-Walker Syndrome / genetics*
  • Encephalocele / genetics*
  • Exome
  • Extracellular Matrix / genetics
  • Humans
  • Laminin / chemistry
  • Laminin / genetics*
  • Laminin / metabolism
  • Membrane Glycoproteins / chemistry
  • Membrane Glycoproteins / genetics*
  • Membrane Glycoproteins / metabolism
  • Mutation*
  • Protein Structure, Tertiary
  • Sequence Analysis, DNA

Substances

  • Laminin
  • Membrane Glycoproteins
  • laminin gamma 1
  • nidogen