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Article: RET mutational spectrum in Hirschsprung disease: Evaluation of 601 Chinese patients
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TitleRET mutational spectrum in Hirschsprung disease: Evaluation of 601 Chinese patients
 
AuthorsSo, MT5
LeonThomas, YY5
Cheng, G5
TangClara, SM5
Miao, XP8
Cornes, BK5
Ngo, DN10
Cui, L5
NganElly, SW5 5
LuiVincent, CH5 5
Wu, XZ2
Wang, B1
Wang, H4
Yuan, ZW3
Huang, LM9
Li, L11
Xia, H6
Zhu, D6
Liu, J7
Nguyen, TL10
ChanIvy, HY5
ChungPatrick, HY5
Liu, XL5
Zhang, R5
WongKenneth, KY5
Sham, PC5 5 5
Cherny, SS5
TamPaul, KH5 5
GarciaBarcelo, MM5 5
 
Keywords5' untranslated region
Chinese
Exon
Gene cluster
Genetic association
 
Issue Date2011
 
PublisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
CitationPlos One, 2011, v. 6 n. 12 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0028986
 
AbstractRare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial). Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5′ untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls. © 2011 So et al.
 
ISSN1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
DOIhttp://dx.doi.org/10.1371/journal.pone.0028986
 
PubMed Central IDPMC3235168
 
ISI Accession Number IDWOS:000298365700085
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 765407M
HKU 778610M
University of Hong Kong200611159028
University of Hong Kong Genomics Strategic Research Theme
Funding Information:

This work was supported by research grants from the Hong Kong Research Grants Council HKU 765407M to M-MG-B and HKU 778610M to PK-HT; and from The University of Hong Kong Seed Funding Programme 200611159028 to M-MG-B. Support was also obtained from The University of Hong Kong Genomics Strategic Research Theme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 
ReferencesReferences in Scopus
 
GrantsDeep Re-Sequencing of Hirschsprung's Disease Candidate Genes
Functional evaluation of RET coding and non-coding sequence mutations in Hirschsprung's disease
 
DC FieldValue
dc.contributor.authorSo, MT
 
dc.contributor.authorLeonThomas, YY
 
dc.contributor.authorCheng, G
 
dc.contributor.authorTangClara, SM
 
dc.contributor.authorMiao, XP
 
dc.contributor.authorCornes, BK
 
dc.contributor.authorNgo, DN
 
dc.contributor.authorCui, L
 
dc.contributor.authorNganElly, SW
 
dc.contributor.authorLuiVincent, CH
 
dc.contributor.authorWu, XZ
 
dc.contributor.authorWang, B
 
dc.contributor.authorWang, H
 
dc.contributor.authorYuan, ZW
 
dc.contributor.authorHuang, LM
 
dc.contributor.authorLi, L
 
dc.contributor.authorXia, H
 
dc.contributor.authorZhu, D
 
dc.contributor.authorLiu, J
 
dc.contributor.authorNguyen, TL
 
dc.contributor.authorChanIvy, HY
 
dc.contributor.authorChungPatrick, HY
 
dc.contributor.authorLiu, XL
 
dc.contributor.authorZhang, R
 
dc.contributor.authorWongKenneth, KY
 
dc.contributor.authorSham, PC
 
dc.contributor.authorCherny, SS
 
dc.contributor.authorTamPaul, KH
 
dc.contributor.authorGarciaBarcelo, MM
 
dc.date.accessioned2012-02-03T06:14:25Z
 
dc.date.available2012-02-03T06:14:25Z
 
dc.date.issued2011
 
dc.description.abstractRare (RVs) and common variants of the RET gene contribute to Hirschsprung disease (HSCR; congenital aganglionosis). While RET common variants are strongly associated with the commonest manifestation of the disease (males; short-segment aganglionosis; sporadic), rare coding sequence (CDS) variants are more frequently found in the lesser common and more severe forms of the disease (females; long/total colonic aganglionosis; familial). Here we present the screening for RVs in the RET CDS and intron/exon boundaries of 601 Chinese HSCR patients, the largest number of patients ever reported. We identified 61 different heterozygous RVs (50 novel) distributed among 100 patients (16.64%). Those include 14 silent, 29 missense, 5 nonsense, 4 frame-shifts, and one in-frame amino-acid deletion in the CDS, two splice-site deletions, 4 nucleotide substitutions and a 22-bp deletion in the intron/exon boundaries and 1 single-nucleotide substitution in the 5′ untranslated region. Exonic variants were mainly clustered in RET the extracellular domain. RET RVs were more frequent among patients with the most severe phenotype (24% vs. 15% in short-HSCR). Phasing RVs with the RET HSCR-associated haplotype suggests that RVs do not underlie the undisputable association of RET common variants with HSCR. None of the variants were found in 250 Chinese controls. © 2011 So et al.
 
dc.description.naturepublished_or_final_version
 
dc.identifier.citationPlos One, 2011, v. 6 n. 12 [How to Cite?]
DOI: http://dx.doi.org/10.1371/journal.pone.0028986
 
dc.identifier.doihttp://dx.doi.org/10.1371/journal.pone.0028986
 
dc.identifier.hkuros198430
 
dc.identifier.isiWOS:000298365700085
Funding AgencyGrant Number
Hong Kong Research Grants CouncilHKU 765407M
HKU 778610M
University of Hong Kong200611159028
University of Hong Kong Genomics Strategic Research Theme
Funding Information:

This work was supported by research grants from the Hong Kong Research Grants Council HKU 765407M to M-MG-B and HKU 778610M to PK-HT; and from The University of Hong Kong Seed Funding Programme 200611159028 to M-MG-B. Support was also obtained from The University of Hong Kong Genomics Strategic Research Theme. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

 
dc.identifier.issn1932-6203
2012 Impact Factor: 3.73
2012 SCImago Journal Rankings: 1.512
 
dc.identifier.issue12
 
dc.identifier.pmcidPMC3235168
 
dc.identifier.pmid22174939
 
dc.identifier.scopuseid_2-s2.0-83055178223
 
dc.identifier.urihttp://hdl.handle.net/10722/144569
 
dc.identifier.volume6
 
dc.languageeng
 
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.action
 
dc.publisher.placeUnited States
 
dc.relation.ispartofPLoS ONE
 
dc.relation.projectDeep Re-Sequencing of Hirschsprung's Disease Candidate Genes
 
dc.relation.projectFunctional evaluation of RET coding and non-coding sequence mutations in Hirschsprung's disease
 
dc.relation.referencesReferences in Scopus
 
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License
 
dc.subject5' untranslated region
 
dc.subjectChinese
 
dc.subjectExon
 
dc.subjectGene cluster
 
dc.subjectGenetic association
 
dc.titleRET mutational spectrum in Hirschsprung disease: Evaluation of 601 Chinese patients
 
dc.typeArticle
 
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Author Affiliations
  1. Shenzhen Children's Hospital
  2. Guiyang Medical College
  3. China Medical University Shenyang
  4. Changchun Centre Hospital
  5. The University of Hong Kong
  6. Guangzhou Women and Children's Medical Centre
  7. Sun Yat-Sen University
  8. Huazhong University of Science and Technology
  9. Beijing Children's Hospital
  10. National Hospital of Pediatrics Hanoi
  11. Capital Institute of Pediatrics