Next generation sequencing of chromosomal rearrangements in patients with split-hand/split-foot malformation provides evidence for DYNC1I1 exonic enhancers of DLX5/6 expression in humans

Lango-Allen and colleagues studied two families with split hand/split foot malformation and looked for causal mutations using new genome-wide sequencing technology. In one family they identified a deletion that included specific protein-coding regions of DYNC1I1 gene, recently shown to regulate DLX5/6 genes in the developing mouse and zebrafish limbs. In the second family there was a physical separation of DYNC1I1 and DLX5/6 genes. Together these results support the role of DYNC1I1 protein-coding regions as regulators of far-away target genes DLX5/6 in human limb development. The study illustrates the application of whole genome sequencing technology for identifying and characterizing chromosomal rearrangements at high resolution. (By Dr. Hana Lango Allen, http://jmg.bmj.com/content/early/2014/01/23/jmedgenet-2013-102142 )