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Science 19 February 1999:
Vol. 283. no. 5405, pp. 1158 - 1161
DOI: 10.1126/science.283.5405.1158
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Reports

A Molecular Pathway Revealing a Genetic Basis for Human Cardiac and Craniofacial Defects

Hiroyuki Yamagishi, 1* Vidu Garg, 1* Rumiko Matsuoka, 3 Tiffani Thomas, 1 Deepak Srivastava 12dagger

Microdeletions of chromosome 22q11 are the most common genetic defects associated with cardiac and craniofacial anomalies in humans. A screen for mouse genes dependent on dHAND, a transcription factor implicated in neural crest development, identified Ufd1, which maps to human 22q11 and encodes a protein involved in degradation of ubiquitinated proteins. Mouse Ufd1 was specifically expressed in most tissues affected in patients with 22q11 deletion syndrome. The human UFD1L gene was deleted in all 182 patients studied with 22q11 deletion, and a smaller deletion of approximately 20 kilobases that removed exons 1 to 3 of UFD1L was found in one individual with features typical of 22q11 deletion syndrome. These data suggest that UFD1L haploinsufficiency contributes to the congenital heart and craniofacial defects seen in 22q11 deletion.

1 Departments of Pediatrics, Division of Cardiology, and
2 Molecular Biology and Oncology, University of Texas Southwestern Medical Center, 6000 Harry Hines Boulevard, Room NA8.124, Dallas, TX 75235-9148, USA.
3 Department of Pediatric Cardiology, The Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: dsriva{at}mednet.swmed.edu

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