JCI table of contents: Nov. 21, 2007(View the PDF of this article at: D...),Health

DEVELOPMENT: Location, location, location: gene determining body organ position identified

Primary ciliary diskinesia (PCD) is an inherited disease caused by mutations in any one of a number of genes, including the gene DNAH5. Individuals with PCD are highly susceptible to chronic recurrent respiratory infections and the left-right positioning of the organs of their body is completely mirror image reversed (i.e., instead of their heart being on the left side of their body it is on the right). Some individuals with PCD exhibit heterotaxy, a condition characterized by randomized left-right organ positioning. It had not been established previously whether the genetic defects that lead to PCD are also responsible for heterotaxy, but new research in mice by Cecelia Lo and colleagues at the National Institutes of Health, Bethesda, has now suggested that this is the case.

In the study, a substantial proportion of fetal mice with a mutation in both copies of their Dnahc5 gene (the mouse equivalent of DNAH5) exhibited heterotaxy and, as observed in human heterotaxy syndromes, these embryos had variable combinations of complex structural heart defects. Further analysis confirmed that these mice were a robust model of PCD, indicating that a Dnahc5 mutation causing PCD-like disease in mice also can cause heterotaxy. These data led the authors to suggest individuals with PCD should be assessed for heterotaxy and associated congenital heart defects, and conversely, patients with heterotaxy should be evaluated for undiagnosed PCD. Such combined diagnoses would dictate very different clinical strategies that may improve outcome.

TITLE: Heterotaxy and complex structural heart defects in a mutant mouse model of primary ciliary dyskinesia

AUTHOR CONTACT:

Cecilia W.
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