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(Circulation Research. 2004;94:1401.)
© 2004 American Heart Association, Inc.

Editorials

Only Our Patients Know for Sure

H. Scott Baldwin

From Vanderbilt Children’s Hospital, Nashville, Tenn.

Correspondence to H. Scott Baldwin, MD, Katrina Overall Professor, Professor of Pediatrics and Cell and Developmental Biology, Vice Chair for Laboratory Sciences in Pediatrics, Vanderbilt Children’s Hospital, B3307 MCN VUMC 1161 21st St South, Nashville, TN 37232-2495. E-mail Scott.Baldwin@vanderbilt.edu

Key Words: congenital heart disease • coarctation • contiguous gene deletion

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Although congenital heart disease (CHD) is frequently associated with syndromes that affect multiple organs, the majority of cases present as isolated CHD, and typically defects are limited to a defined structure, suggesting a unique developmental mechanism. Despite the frequent occurrence of CHD, relatively few causative genes have been clearly identified (see review¹). In this issue of Circulation Research, Christiansen et al²describe the occurrence of isolated (nonsyndromic) CHD in association with the deletion of a 1.5- to 3-mB region on chromosome 1q21.1 They suggest that the cardiac defects seen represent a contiguous gene deletion syndrome and cannot be explained by the deletion of any one gene located within the region. Notably, they present patients with isolated coarctation and interrupted aortic arch (IAA) type A.

But why does a contiguous gene hypothesis have to be invoked? In the three patients presented, a spectrum of left ventricular outflow tract obstruction, including subaortic stenosis and IAA, in addition to ventricular septal defect (VSD) and aortopulmonary window, is represented. All of these abnormalities have been experimentally linked to defects in neural crest ontogeny. Likewise, deletion of connexin40 (Cx40) in mice is associated with a high incidence of conotruncal abnormalities including Tetralogy of Fallot, double outlet right ventricle, and abnormal branching of the aortic arch.^3,4 These similarly implicate abnormalities of neural crest migration.⁵

It would be tempting to try and unify the phenotypes observed by suggesting a single gene defect altering neural crest ontogeny. However, a closer look at the specific patient phenotypes . . . [Full Text of this Article]