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Article: RET mutational spectrum in Hirschsprung disease: Evaluation of 601 Chinese patients

TitleRET mutational spectrum in Hirschsprung disease: Evaluation of 601 Chinese patients
Authors
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
Citation
Plos One, 2011, v. 6 n. 12 How to Cite?
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.
Persistent Identifierhttp://hdl.handle.net/10722/144569
ISSN
2014 Impact Factor: 3.234
2013 SCImago Journal Rankings: 1.724
PubMed Central ID
ISI Accession Number ID
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.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorSo, MTen_HK
dc.contributor.authorLeonThomas, YYen_HK
dc.contributor.authorCheng, Gen_HK
dc.contributor.authorTangClara, SMen_HK
dc.contributor.authorMiao, XPen_HK
dc.contributor.authorCornes, BKen_HK
dc.contributor.authorNgo, DNen_HK
dc.contributor.authorCui, Len_HK
dc.contributor.authorNganElly, SWen_HK
dc.contributor.authorLuiVincent, CHen_HK
dc.contributor.authorWu, XZen_HK
dc.contributor.authorWang, Ben_HK
dc.contributor.authorWang, Hen_HK
dc.contributor.authorYuan, ZWen_HK
dc.contributor.authorHuang, LMen_HK
dc.contributor.authorLi, Len_HK
dc.contributor.authorXia, Hen_HK
dc.contributor.authorZhu, Den_HK
dc.contributor.authorLiu, Jen_HK
dc.contributor.authorNguyen, TLen_HK
dc.contributor.authorChanIvy, HYen_HK
dc.contributor.authorChungPatrick, HYen_HK
dc.contributor.authorLiu, XLen_HK
dc.contributor.authorZhang, Ren_HK
dc.contributor.authorWongKenneth, KYen_HK
dc.contributor.authorSham, PCen_HK
dc.contributor.authorCherny, SSen_HK
dc.contributor.authorTamPaul, KHen_HK
dc.contributor.authorGarciaBarcelo, MMen_HK
dc.date.accessioned2012-02-03T06:14:25Z-
dc.date.available2012-02-03T06:14:25Z-
dc.date.issued2011en_HK
dc.identifier.citationPlos One, 2011, v. 6 n. 12en_HK
dc.identifier.issn1932-6203en_HK
dc.identifier.urihttp://hdl.handle.net/10722/144569-
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.en_HK
dc.languageengen_US
dc.publisherPublic Library of Science. The Journal's web site is located at http://www.plosone.org/home.actionen_HK
dc.relation.ispartofPLoS ONEen_HK
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 patientsen_HK
dc.typeArticleen_HK
dc.identifier.emailSham, PC: pcsham@hku.hken_HK
dc.identifier.emailCherny, SS: cherny@hku.hken_HK
dc.identifier.emailGarciaBarcelo, MM: mmgarcia@hku.hken_HK
dc.identifier.authoritySham, PC=rp00459en_HK
dc.identifier.authorityCherny, SS=rp00232en_HK
dc.identifier.authorityGarciaBarcelo, MM=rp00445en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1371/journal.pone.0028986en_HK
dc.identifier.pmid22174939-
dc.identifier.pmcidPMC3235168-
dc.identifier.scopuseid_2-s2.0-83055178223en_HK
dc.identifier.hkuros198430en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-83055178223&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume6en_HK
dc.identifier.issue12en_HK
dc.identifier.isiWOS:000298365700085-
dc.publisher.placeUnited Statesen_HK
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.identifier.scopusauthoridSo, MT=8748542200en_HK
dc.identifier.scopusauthoridLeonThomas, YY=54581214400en_HK
dc.identifier.scopusauthoridCheng, G=37861100700en_HK
dc.identifier.scopusauthoridTangClara, SM=54581695600en_HK
dc.identifier.scopusauthoridMiao, XP=7102585391en_HK
dc.identifier.scopusauthoridCornes, BK=8083360800en_HK
dc.identifier.scopusauthoridNgo, DN=54581363100en_HK
dc.identifier.scopusauthoridCui, L=54580785400en_HK
dc.identifier.scopusauthoridNganElly, SW=54581287800en_HK
dc.identifier.scopusauthoridLuiVincent, CH=54581229100en_HK
dc.identifier.scopusauthoridWu, XZ=36553563000en_HK
dc.identifier.scopusauthoridWang, B=54581823200en_HK
dc.identifier.scopusauthoridWang, H=54581767200en_HK
dc.identifier.scopusauthoridYuan, ZW=10641253300en_HK
dc.identifier.scopusauthoridHuang, LM=12647222900en_HK
dc.identifier.scopusauthoridLi, L=54581233500en_HK
dc.identifier.scopusauthoridXia, H=54581752700en_HK
dc.identifier.scopusauthoridZhu, D=22936543500en_HK
dc.identifier.scopusauthoridLiu, J=54581116500en_HK
dc.identifier.scopusauthoridNguyen, TL=24367129600en_HK
dc.identifier.scopusauthoridChanIvy, HY=54580749300en_HK
dc.identifier.scopusauthoridChungPatrick, HY=54580723000en_HK
dc.identifier.scopusauthoridLiu, XL=37461750900en_HK
dc.identifier.scopusauthoridZhang, R=45261666800en_HK
dc.identifier.scopusauthoridWongKenneth, KY=54581867300en_HK
dc.identifier.scopusauthoridSham, PC=34573429300en_HK
dc.identifier.scopusauthoridCherny, SS=7004670001en_HK
dc.identifier.scopusauthoridTamPaul, KH=54581573900en_HK
dc.identifier.scopusauthoridGarciaBarcelo, MM=6701767303en_HK

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