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 > 4000 DNA variants and implicated a single gene, WDR62, as harboring potentially deleterious changes. We subsequently identified additional WDR62 mutations in four other families. MRI and postmortem brain analysis supports important roles for WDR62 in proliferation and migration of neuronal precursors. WDR62 is a WD40 repeat-containing protein expressed in neuronal precursors as well as postmitotic neurons in the developing brain and localizes to the spindle poles of dividing cells. The diverse phenotypes of WDR62 suggest central roles in many aspects of cerebral cortical development.

These novel piglet models of short bowel syndrome are the first to represent the full clinical spectrum of intestinal failure as observed in human neonates. By considering the impact of different short bowel anatomy on potential for adaptation and growth, these animal models are a significant advance. They permit evaluation of new therapies to promote intestinal adaptation and reduce complications, such as cholestasis.