UDP-glucose Dehydrogenase Polymorphisms from Patients with Congenital Heart Valve Defects Disrupt Enzyme Stability and Quaternary Assembly

Authors

Annastasia S. Hyde, University of Nebraska-Lincoln
Erin L. Farmer, University of Nebraska-Lincoln
Katherine E. Easley, University of Nebraska-Lincoln
Kristy van Lammeren, ubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW)
Vincent M. Christoffels, University of Amsterdam
Joseph J. Barycki, University of Nebraska - LincolnFollow
Jeroen Bakkers, ubrecht Institute, Royal Netherlands Academy of Arts and Sciences (KNAW)
Melanie A. Simpson, University of Nebraska- LincolnFollow

Document Type

Article

Date of this Version

2012

Citation

THE JOURNAL OF BIOLOGICAL CHEMISTRY VOL. 287, NO. 39, pp. 32708–32716, September 21, 2012

DOI 10.1074/jbc.M112.395202

Comments

© 2012 by The American Society for Biochemistry and Molecular Biology, Inc

Abstract

Background: UDP-glucose dehydrogenase (UGDH) polymorphisms were identified in a screen of candidate genes for heart valve defects.

Results: Two individual mutants fail to rescue cardiac valve defects in UGDH-deleted zebrafish and have reduced stability in vitro.

Conclusion: UGDH loss of function mutations result in a subset of human congenital cardiac valve defects caused by reduced enzyme activity during morphogenesis.

Significance: Screening these alleles could predict valve defects.