Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant dandy-walker malformation and occipital cephaloceles

Benjamin W. Darbro, Vinit B. Mahajan, Lokesh Gakhar, Jessica M. Skeie, Elizabeth Campbell, Shu Wu, Xinyu Bing, Kathleen J. Millen, William B. Dobyns, John A. Kessler, Ali Jalali, James Cremer, Alberto Segre, J. Robert Manak, Kimerbly A. Aldinger, Satoshi Suzuki, Nagato Natsume, Maya Ono, Huynh Dai Hai, Le Thi VietSara Loddo, Enza M. Valente, Laura Bernardini, Nitin Ghonge, Polly J. Ferguson, Alexander G. Bassuk

Research output: Contribution to journalArticle

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.

Original languageEnglish
Pages (from-to)1075-1079
Number of pages5
JournalHuman Mutation
Volume34
Issue number8
DOIs
Publication statusPublished - Aug 2013

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Keywords

  • Dandy-Walker
  • Exome
  • Extracellular matrix
  • LAMC1
  • NID1

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Darbro, B. W., Mahajan, V. B., Gakhar, L., Skeie, J. M., Campbell, E., Wu, S., Bing, X., Millen, K. J., Dobyns, W. B., Kessler, J. A., Jalali, A., Cremer, J., Segre, A., Manak, J. R., Aldinger, K. A., Suzuki, S., Natsume, N., Ono, M., Hai, H. D., ... Bassuk, A. G. (2013). Mutations in extracellular matrix genes NID1 and LAMC1 cause autosomal dominant dandy-walker malformation and occipital cephaloceles. Human Mutation, 34(8), 1075-1079. https://doi.org/10.1002/humu.22351