The laterality in the embryo is determined by left-right asymmetric gene expression driven by the flow of extraembryonic fluid which is maintained by the rotary movement of monocilia on the nodal cells. Defects manifest by abnormal formation and arrangement of visceral organs. The genetic etiology of defects not associated with primary ciliary dyskinesia is largely unknown. In this study we investigated the cause of situs anomalies, including heterotaxy syndrome and situs inversus totalis, in a consanguineous family. Whole exome analysis revealed a homozygous deleterious deletion in the WDR16 gene which segregated with the phenotype. WDR16 protein was previously proposed to play a role in cilia-related signal transduction processes; the rat Wdr16 protein was shown to be confined to cilia possessing tissues and severe hydrocephalus was observed in the wdr16 gene knockdown zebrafish. The phenotype associated with the homozygous deletion in our patients suggests a role for WDR16 in human laterality patterning. The present report underscores the importance of coverage data analysis as part of Exome sequencing in detecting large copy number variants. Exome analysis is a valuable tool for molecular investigation even in cases of large deletions.
