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
LuiVincent, CH5
Wu, XZ3
Wang, B2
Wang, H4
Yuan, ZW1
Huang, LM9
Li, L11
Xia, H6
Zhu, D6
Liu, J7
Nguyen, TL10
ChanIvy, HY5
ChungPatrick, HY5
Liu, XL5
Zhang, R5
WongKenneth, KY5
Sham, PC5
Cherny, SS5
TamPaul, KH5
GarciaBarcelo, MM5
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
2011 Impact Factor: 4.092
2011 SCImago Journal Rankings: 0.519
DOIhttp://dx.doi.org/10.1371/journal.pone.0028986
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.

PubMed Central IDPMC3235168
ReferencesReferences in Scopus
GrantsDeep Re-Sequencing of Hirschsprung's Disease Candidate Genes
Functional analysis of RET coding region mutations
Functional evaluation of RET coding and non-coding sequence mutations in Hirschsprung's disease
DC Field
Value
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.grantDeep Re-Sequencing of Hirschsprung's Disease Candidate Genes
dc.description.grantFunctional analysis of RET coding region mutations
dc.description.grantFunctional evaluation of RET coding and non-coding sequence mutations in Hirschsprung's disease
dc.description.grantcode103536
dc.description.grantcode96043
dc.description.grantcode96818
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
2011 Impact Factor: 4.092
2011 SCImago Journal Rankings: 0.519
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.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
Author Affiliations
  1. China Medical University
  2. Shenzhen Children's Hospital
  3. Guiyang Medical College
  4. null
  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