SELECTED ARTICLES FROM THE RECENT LITERATURE 2007

November 2, 2007

Genetic mosaicism, not spontaneous mutation, can result in hereditary angioedema in the absence of a history of symptoms in parents

Summary
We have all seen patients with hereditary angioedema (exhibiting classically low levels of C1 inhibitor) whose parents did not have this disease. Since it is normally inherited as an autosomal dominant condition, such patients were thought to be spontaneous mutations. However, in this interesting article, the father, although having normal C1 inhibitor levels, carried the same mutation in the C1 inhibitor gene as his progeny, who had low levels of C1 inhibitor and classical findings for the disease state. The father was not affected because he demonstrated genetic mosaicism. Mosaicism refers to a condition in which an individual has two or more cell populations differing in genetic makeup. It can occur because of an error in cell division early in fetal development. In this instance, the "normal" portion of the mosaicism was sufficient to allow the father to have relatively normal C1 inhibitor levels, and thus protect him from the disease. However, all three sons had low levels of the inhibitor, and two of the three experienced symptoms.

Editor's Comments
The importance of this article is related to the fact that the clinician cannot automatically rule out hereditary angioedema in the absence of symptoms in the mother or father, and mosaicism, rather than spontaneous mutation, may be the cause of this phenomenon.

Reference
Yu T, et al. Paternal mosaicism and hereditary angioedema in a Taiwanese family. Annals of Allergy, Asthma, and Immunology 2007; 99(4):375-379.

 

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