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

ABSTRACT: 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

SUBMITTER: Yu TW 

PROVIDER: S-EPMC2969850 | biostudies-literature | 2010 Nov

REPOSITORIES: biostudies-literature