De novo mutations in the actin genes ACTB and ACTG1 cause Baraitser-Winter syndrome Academic Article uri icon

Overview

MeSH Major

  • Abnormalities, Multiple
  • Actins
  • Brain

abstract

  • Brain malformations are individually rare but collectively common causes of developmental disabilities. Many forms of malformation occur sporadically and are associated with reduced reproductive fitness, pointing to a causative role for de novo mutations. Here, we report a study of Baraitser-Winter syndrome, a well-defined disorder characterized by distinct craniofacial features, ocular colobomata and neuronal migration defect. Using whole-exome sequencing of three proband-parent trios, we identified de novo missense changes in the cytoplasmic actin-encoding genes ACTB and ACTG1 in one and two probands, respectively. Sequencing of both genes in 15 additional affected individuals identified disease-causing mutations in all probands, including two recurrent de novo alterations (ACTB, encoding p.Arg196His, and ACTG1, encoding p.Ser155Phe). Our results confirm that trio-based exome sequencing is a powerful approach to discover genes causing sporadic developmental disorders, emphasize the overlapping roles of cytoplasmic actin proteins in development and suggest that Baraitser-Winter syndrome is the predominant phenotype associated with mutation of these two genes.

authors

publication date

  • April 2012

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3677859

Digital Object Identifier (DOI)

  • 10.1038/ng.1091

PubMed ID

  • 22366783

Additional Document Info

start page

  • 440

end page

  • 4, S1-2

volume

  • 44

number

  • 4