title: A human laterality disorder associated with a homozygous WDR16 deletion.
abstract: 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. Exome analysis is a valuable tool for molecular investigation even in cases of large deletions.
authors.affiliation: Department of Pediatric Cardiology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Asaf
authors.initials: A
authors.lastname: Ta-Shma
authors.affiliation: Department of Pediatric Cardiology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Zeev
authors.initials: Z
authors.lastname: Perles
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Barak
authors.initials: B
authors.lastname: Yaacov
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Marion
authors.initials: M
authors.lastname: Werner
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Ayala
authors.initials: A
authors.lastname: Frumkin
authors.affiliation: Department of Pediatric Cardiology, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Azaria J J T
authors.initials: AJ
authors.lastname: Rein
authors.affiliation: Monique and Jacques Roboh Department of Genetic Research, Hadassah, Hebrew University Medical Center, Jerusalem, Israel.
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D005260:Female; D006801:Humans; D007223:Infant; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D002923:Cilia; D003241:Consanguinity; D059472:Exome; D059446:Heterotaxy Syndrome / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006720:Homozygote; D006849:Hydrocephalus / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000662:veterinary; D007979:Levocardia / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008969:Molecular Sequence Data; D010641:Phenotype; D017422:Sequence Analysis, DNA; D017384:Sequence Deletion; D000818:Animals; D051381:Rats
chemical_list: D002352:Carrier Proteins; C503847:CFAP52 protein, human