Article: Functional analyses of RET mutations in Chinese hirschsprung disease patients
| Title | Functional analyses of RET mutations in Chinese hirschsprung disease patients | ||||||
|---|---|---|---|---|---|---|---|
| Authors | Leon, TYY So, MT1 Lui, VCH1 Hofstra, RMW Tam, PKH1 Ngan, ESW1 Garcia-Barcelo, MM1 | ||||||
| Keywords | RET Mutation Megacolon Hirschsprung Aganglionosis | ||||||
| Issue Date | 2012 | ||||||
| Publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/102526943 | ||||||
| Citation | Birth Defects Research Part A: Clinical and Molecular Teratology, 2012, v. 94 n. 1, p. 47-51 [How to Cite?] DOI: http://dx.doi.org/10.1002/bdra.22863 | ||||||
| Abstract | BACKGROUND: 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. CONCLUSION: 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. © 2011 Wiley Periodicals, Inc. | ||||||
| ISSN | 1542-0752 2011 SCImago Journal Rankings: 0.199 | ||||||
| DOI | http://dx.doi.org/10.1002/bdra.22863 | ||||||
| ISI Accession Number ID | WOS:000298951600008
Funding Information: 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-Merce Garcia-Barcelo. | ||||||
| References | References in Scopus |
| dc.contributor.author | Leon, TYY | ||||||
|---|---|---|---|---|---|---|---|
| dc.contributor.author | So, MT | ||||||
| dc.contributor.author | Lui, VCH | ||||||
| dc.contributor.author | Hofstra, RMW | ||||||
| dc.contributor.author | Tam, PKH | ||||||
| dc.contributor.author | Ngan, ESW | ||||||
| dc.contributor.author | Garcia-Barcelo, MM | ||||||
| dc.date.accessioned | 2012-03-27T09:03:54Z | ||||||
| dc.date.available | 2012-03-27T09:03:54Z | ||||||
| dc.date.issued | 2012 | ||||||
| dc.description.abstract | BACKGROUND: 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. CONCLUSION: 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. © 2011 Wiley Periodicals, Inc. | ||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||
| dc.identifier.citation | Birth Defects Research Part A: Clinical and Molecular Teratology, 2012, v. 94 n. 1, p. 47-51 [How to Cite?] DOI: http://dx.doi.org/10.1002/bdra.22863 | ||||||
| dc.identifier.doi | http://dx.doi.org/10.1002/bdra.22863 | ||||||
| dc.identifier.epage | 51 | ||||||
| dc.identifier.hkuros | 198846 | ||||||
| dc.identifier.isi | WOS:000298951600008
Funding Information: 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-Merce Garcia-Barcelo. | ||||||
| dc.identifier.issn | 1542-0752 2011 SCImago Journal Rankings: 0.199 | ||||||
| dc.identifier.issue | 1 | ||||||
| dc.identifier.pmid | 22131258 | ||||||
| dc.identifier.scopus | eid_2-s2.0-84855736120 | ||||||
| dc.identifier.spage | 47 | ||||||
| dc.identifier.uri | http://hdl.handle.net/10722/145951 | ||||||
| dc.identifier.volume | 94 | ||||||
| dc.language | eng | ||||||
| dc.publisher | John Wiley & Sons, Inc. The Journal's web site is located at http://www3.interscience.wiley.com/cgi-bin/jhome/102526943 | ||||||
| dc.publisher.place | United States | ||||||
| dc.relation.ispartof | Birth Defects Research Part A: Clinical and Molecular Teratology | ||||||
| dc.relation.references | References in Scopus | ||||||
| dc.rights | Birth Defects Research Part A: Clinical and Molecular Teratology. Copyright © John Wiley & Sons, Inc. | ||||||
| dc.subject.mesh | Asian continental ancestry group - genetics | ||||||
| dc.subject.mesh | Hirschsprung disease - genetics | ||||||
| dc.subject.mesh | Mutation | ||||||
| dc.subject.mesh | Penetrance | ||||||
| dc.subject.mesh | Proto-oncogene proteins c-RET - genetics - metabolism | ||||||
| dc.subject | RET | ||||||
| dc.subject | Mutation | ||||||
| dc.subject | Megacolon | ||||||
| dc.subject | Hirschsprung | ||||||
| dc.subject | Aganglionosis | ||||||
| dc.title | Functional analyses of RET mutations in Chinese hirschsprung disease patients | ||||||
| dc.type | Article |
Author Affiliations
- The University of Hong Kong
- Universitair Medisch Centrum Groningen