These authors contributed equally to this work.
Article first published online: 1 DEC 2011
Copyright © 2011 Wiley Periodicals, Inc.
Birth Defects Research Part A: Clinical and Molecular Teratology
Volume 94, Issue 1, pages 47–51, January 2012
How to Cite
Leon, T. Y.Y., So, M.-T., Lui, V. C.H., Hofstra, R. M.W., Tam, P. K.H., Ngan, E. S.W. and Garcia-Barceló, M.-M. (2012), Functional analyses of RET mutations in Chinese hirschsprung disease patients. Birth Defects Research Part A: Clinical and Molecular Teratology, 94: 47–51. doi: 10.1002/bdra.22863
This work was supported by research grants from the Hong Kong Research Grants Council (765407M) and the University of Hong Kong Seed Funding Programme for Basic Research to Maria-Mercè Garcia–Barcelo.
- Issue published online: 10 JAN 2012
- Article first published online: 1 DEC 2011
- Manuscript Accepted: 25 AUG 2011
- Manuscript Revised: 17 AUG 2011
- Manuscript Received: 13 JUL 2011
Hirschsprung disease (HSCR) is a congenital disease characterized by the absence of ganglion cells in various length of distal digestive tract. The rearranged during transfection gene (RET) is considered the major gene in HSCR. Although an increasing number of HSCR-associated RET coding sequence (CDS) mutations have been identified in recent years, not many have been investigated for functional consequence on the RET protein.
METHODS and RESULTS
We examined the functional implications of the de novo RET-CDS mutations V145G, Y483X, V636fsX1, and F961L that we first identified in sporadic Chinese patients with HSCR. The V145G disrupted RET glycosylation and F961L RET phosphorylation. Presumably, the truncation mutations would affect the translocation or the anchoring of the RET protein onto the cellular membrane.
The study of RET-CDS mutations that appear de novo is essential not only for understanding the mechanistic of the disease but also for penetrance and recurrence risk estimations, being the ultimate goal for the improvement in disease management and counseling. Birth Defects Research (Part A), 2012. © 2011 Wiley Periodicals, Inc.