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(Circulation Research. 1999;84:127-135.)
© 1999 American Heart Association, Inc.

Original Contribution

HIRA, a DiGeorge Syndrome Candidate Gene, Is Required for Cardiac Outflow Tract Septation

Michael J. Farrell, Harriett Stadt, Kathleen T. Wallis, Peter Scambler, R. Lester Hixon, Raymond Wolfe, Linda Leatherbury, Margaret L. Kirby

From the Developmental Biology Program, Institute of Molecular Medicine, Medical College of Georgia (M.J.F., H.S., K.T.W., R.L.H., R.W., L.L., M.L.K.), Augusta, Ga, and Institute of Child Health (P.S.), London, United Kingdom.

Correspondence to Margaret L. Kirby, PhD, at Institute of Molecular Medicine, Medical College of Georgia, Augusta, GA 30912-2640. E-mail mkirby{at}mail.mcg.edu

Abstract—DiGeorge syndrome (DGS) is a congenital disease characterized by defects in organs and tissues that depend on contributions by cell populations derived from neural crest for proper development. A number of candidate genes that lie within the q11 region of chromosome 22 commonly deleted in DGS patients have been identified. Orthologues of the DGS candidate gene HIRA are expressed in the neural crest and in neural crest–derived tissues in both chick and mouse embryos. By exposing a portion of the premigratory chick neural crest to phosphorothioate end–protected antisense oligonucleotides, ex ovo, followed by orthotopic backtransplantation to the untreated embryos, we have shown that the functional attenuation of cHIRA in the chick cardiac neural crest results in a significantly increased incidence of persistent truncus arteriosus, a phenotypic change characteristic of DGS, but does not affect the repatterning aortic arch arteries, the ventricular function, or the alignment of the outflow tract.

Key Words: DiGeorge syndrome • HIRA • persistent truncus arteriosus

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