Disorders of left–right asymmetry: Heterotaxy and situs inversus
- 28 October 2009
- journal article
- review article
- Published by Wiley in Seminars in Medical Genetics, Part C of the American Journal of Medical Genetics
- Vol. 151C (4), 307-317
- https://doi.org/10.1002/ajmg.c.30228
Abstract
Cilia function is critical to the development of proper organ laterality. Primary ciliary dyskinesia (PCD) causes randomization of situs. Heterotaxy, or situs ambiguus, is an abnormal arrangement of the thoracic and abdominal organs that results in congenital anomalies. Animal models and developmental biological approaches have defined pathways required during embryogenesis for proper left–right pattern formation. New candidates for genetic causes of human laterality disorders have emerged from recent studies on the assembly, transport, and signaling functions of cilia at the node as well as identification of cilia within the developing heart. There is evidence that deleterious genetic variants within one or more developmental pathways may disrupt signaling in a synergistic or combinatorial fashion to cause congenital anomalies. The molecular pathways underlying PCD and heterotaxy are being discovered at a rapid pace, and there is increasing recognition of the overlap between these two categories of laterality disorders and their relationship to isolated cardiovascular malformations. This review focuses on the clinical manifestations, molecular mechanisms, and human genetics of these disorders of laterality.Keywords
This publication has 109 references indexed in Scilit:
- Perspectives and open problems in the early phases of left–right patterningSeminars in Cell & Developmental Biology, 2009
- Ktu/PF13 is required for cytoplasmic pre-assembly of axonemal dyneinsNature, 2008
- DNAI2 Mutations Cause Primary Ciliary Dyskinesia with Defects in the Outer Dynein ArmAmerican Journal of Human Genetics, 2008
- Monocilia in the embryonic mouse heart suggest a direct role for cilia in cardiac morphogenesisDevelopmental Dynamics, 2008
- Morphogenesis of the node and notochord: The cellular basis for the establishment and maintenance of left–right asymmetry in the mouseDevelopmental Dynamics, 2008
- Reduced NODAL Signaling Strength via Mutation of Several Pathway Members Including FOXH1 Is Linked to Human Heart Defects and HoloprosencephalyAmerican Journal of Human Genetics, 2008
- The Chirality of Gut Rotation Derives from Left-Right Asymmetric Changes in the Architecture of the Dorsal MesenteryDevelopmental Cell, 2008
- Baf60c is a nuclear Notch signaling component required for the establishment of left–right asymmetryProceedings of the National Academy of Sciences of the United States of America, 2007
- Hedgehog signalling in the mouse requires intraflagellar transport proteinsNature, 2003
- Intraflagellar transportNature Reviews Molecular Cell Biology, 2002