European journal of human genetics : EJHG, 2015-09, Vol.23 (9), p.1262-1265
2015
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- Autor(en) / Beteiligte
- Titel
- A human laterality disorder associated with a homozygous WDR16 deletion
- Ist Teil von
- European journal of human genetics : EJHG, 2015-09, Vol.23 (9), p.1262-1265
- Ort / Verlag
- England: Nature Publishing Group
- Erscheinungsjahr
- 2015
- Quelle
- Open access e-journals list
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1018-4813eISSN: 1476-5438DOI: 10.1038/ejhg.2014.265Titel-ID: cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4538206
- Format
- –
- Schlagworte
- Abdomen, Asymmetry, Base Sequence, Cardiology, Cardiovascular disease, Carrier Proteins - genetics, Carrier Proteins - metabolism, Cilia, Clonal deletion, Congenital diseases, Consanguinity, Danio rerio, Defects, Dyskinesia, Embryos, Etiology, Exome, Female, Fluid flow, Gene deletion, Gene expression, Genetics, Heart, Heterotaxy Syndrome - genetics, Heterotaxy Syndrome - metabolism, Heterotaxy Syndrome - pathology, Homozygote, Humans, Hydrocephalus, Hydrocephalus - genetics, Hydrocephalus - metabolism, Hydrocephalus - pathology, Hydrocephalus - veterinary, Infant, Levocardia - genetics, Levocardia - metabolism, Levocardia - pathology, Molecular Sequence Data, Mutation, Patients, Pediatrics, Phenotype, Phenotypes, Primary ciliary dyskinesia, Proteins, Sequence Analysis, DNA, Sequence Deletion, Short Report, Signal transduction, Transduction, Transfer RNA