Mutations in WDR62, encoding a centrosome-associated protein, cause microcephaly with simplified gyri and abnormal cortical architecture.

Published

Journal Article

Genes associated with human microcephaly, a condition characterized by a small brain, include critical regulators of proliferation, cell fate and DNA repair. We describe a syndrome of congenital microcephaly and diverse defects in cerebral cortical architecture. Genome-wide linkage analysis in two families identified a 7.5-Mb locus on chromosome 19q13.12 containing 148 genes. Targeted high throughput sequence analysis of linked genes in each family yielded > 4,000 DNA variants and implicated a single gene, WDR62, as harboring potentially deleterious changes. We subsequently identified additional WDR62 mutations in four other families. Magnetic resonance imaging and postmortem brain analysis supports important roles for WDR62 in the proliferation and migration of neuronal precursors. WDR62 is a WD40 repeat-containing protein expressed in neuronal precursors as well as in postmitotic neurons in the developing brain and localizes to the spindle poles of dividing cells. The diverse phenotypes of WDR62 suggest it has central roles in many aspects of cerebral cortical development.

Full Text

Duke Authors

Cited Authors

  • Yu, TW; Mochida, GH; Tischfield, DJ; Sgaier, SK; Flores-Sarnat, L; Sergi, CM; Topçu, M; McDonald, MT; Barry, BJ; Felie, JM; Sunu, C; Dobyns, WB; Folkerth, RD; Barkovich, AJ; Walsh, CA

Published Date

  • November 2010

Published In

Volume / Issue

  • 42 / 11

Start / End Page

  • 1015 - 1020

PubMed ID

  • 20890278

Pubmed Central ID

  • 20890278

Electronic International Standard Serial Number (EISSN)

  • 1546-1718

Digital Object Identifier (DOI)

  • 10.1038/ng.683

Language

  • eng

Conference Location

  • United States