To test the hypothesis that humans with abnormal cortical development and mental retardation may have null or hypomorphic mutations in NR2E1, we searched for candidate mutations by sequencing the complete coding region, 5′- and 3′-untranslated (UTR), splice site, proximal promoter and evolutionarily conserved non-coding regions in 56 unrelated patients with unexplained congenital microcephaly, a neurodevelopmental disorder characterized by marked reduction in cortical size that may result from failure of neurogenesis (Dobyns 2002; Mochida & Walsh 2001). This evidence concerns the gene NR2E1 and microcephaly.