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Article: Association study of PHOX2B as a candidate gene for Hirschsprung's disease

TitleAssociation study of PHOX2B as a candidate gene for Hirschsprung's disease
Authors
KeywordsMolecular Sequence Numbers
Issue Date2003
PublisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/
Citation
Gut, 2003, v. 52 n. 4, p. 563-567 How to Cite?
AbstractBackground: Hirschsprung's disease (HSCR) is a congenital disorder characterised by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. Manifestation of the disease has been linked to mutations in genes that encode the crucial signals for the development of the enteric nervous system - the RET and EDNRB signalling pathways. The Phox2b gene is involved in neurogenesis and regulates Ret expression in mice, in which disruption of the Phox2b results in a HSCR-like phenotype. Aims: To investigate the contribution of PHOX2B to the HSCR phenotype. Methods: Using polymerase chain reaction amplification and direct sequencing, we screened PHOX2B coding regions and intron/exon boundaries for mutations and polymorphisms in 91 patients with HSCR and 71 ethnically matched controls. Seventy five HSCR patients with no RET mutations were independently considered. Haplotype and genotype frequencies were compared using the standard case control statistic. Results: Sequence analysis revealed three new polymorphisms: two novel single nucleotide polymorphisms (A→G1364; A→C2607) and a 15 base pair deletion (DEL2609). Statistically significant differences were found for A→G1364. Genotypes comprising allele G were underrepresented in patients (19% v 36%; χ2=9.30; p=0.0095 and 22% v 36%; χ2=7.38; p=0.024 for patients with no RET mutations). Pairwise linkage disequilibrium (LD) analysis revealed no LD between physically close polymorphisms indicating a hot spot for recombination in exon 3. Conclusion: The PHOX2B A→G1364 polymorphism is associated with HSCR. Whether it directly contributes to disease susceptibility or represents a marker for a locus in LD with PHOX2B needs further investigation. Our findings are in accordance with the involvement of PHOX2B in the signalling pathways governing the development of enteric neurones.
Persistent Identifierhttp://hdl.handle.net/10722/42616
ISSN
2015 Impact Factor: 14.921
2015 SCImago Journal Rankings: 6.474
PubMed Central ID
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorGarciaBarceló, Men_HK
dc.contributor.authorSham, MHen_HK
dc.contributor.authorLui, VCHen_HK
dc.contributor.authorChen, BLSen_HK
dc.contributor.authorOtt, Jen_HK
dc.contributor.authorTam, PKHen_HK
dc.date.accessioned2007-03-23T04:27:55Z-
dc.date.available2007-03-23T04:27:55Z-
dc.date.issued2003en_HK
dc.identifier.citationGut, 2003, v. 52 n. 4, p. 563-567en_HK
dc.identifier.issn0017-5749en_HK
dc.identifier.urihttp://hdl.handle.net/10722/42616-
dc.description.abstractBackground: Hirschsprung's disease (HSCR) is a congenital disorder characterised by an absence of ganglion cells in the nerve plexuses of the lower digestive tract. Manifestation of the disease has been linked to mutations in genes that encode the crucial signals for the development of the enteric nervous system - the RET and EDNRB signalling pathways. The Phox2b gene is involved in neurogenesis and regulates Ret expression in mice, in which disruption of the Phox2b results in a HSCR-like phenotype. Aims: To investigate the contribution of PHOX2B to the HSCR phenotype. Methods: Using polymerase chain reaction amplification and direct sequencing, we screened PHOX2B coding regions and intron/exon boundaries for mutations and polymorphisms in 91 patients with HSCR and 71 ethnically matched controls. Seventy five HSCR patients with no RET mutations were independently considered. Haplotype and genotype frequencies were compared using the standard case control statistic. Results: Sequence analysis revealed three new polymorphisms: two novel single nucleotide polymorphisms (A→G1364; A→C2607) and a 15 base pair deletion (DEL2609). Statistically significant differences were found for A→G1364. Genotypes comprising allele G were underrepresented in patients (19% v 36%; χ2=9.30; p=0.0095 and 22% v 36%; χ2=7.38; p=0.024 for patients with no RET mutations). Pairwise linkage disequilibrium (LD) analysis revealed no LD between physically close polymorphisms indicating a hot spot for recombination in exon 3. Conclusion: The PHOX2B A→G1364 polymorphism is associated with HSCR. Whether it directly contributes to disease susceptibility or represents a marker for a locus in LD with PHOX2B needs further investigation. Our findings are in accordance with the involvement of PHOX2B in the signalling pathways governing the development of enteric neurones.en_HK
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dc.languageengen_HK
dc.publisherBMJ Publishing Group. The Journal's web site is located at http://gut.bmjjournals.com/en_HK
dc.relation.ispartofGuten_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.rightsGut. Copyright © B M J Publishing Group.en_HK
dc.subjectMolecular Sequence Numbersen_US
dc.subject.meshGenetic predisposition to diseaseen_HK
dc.subject.meshHirschsprung disease - geneticsen_HK
dc.subject.meshHomeodomain proteins - geneticsen_HK
dc.subject.meshTranscription factors - geneticsen_HK
dc.subject.meshDna mutational analysisen_HK
dc.titleAssociation study of PHOX2B as a candidate gene for Hirschsprung's diseaseen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0017-5749&volume=52&issue=4&spage=563&epage=567&date=2003&atitle=Association+study+of+PHOX2B+as+a+candidate+gene+for+Hirschsprung%27s+diseaseen_HK
dc.identifier.emailGarciaBarceló, M: mmgarcia@hkucc.hku.hken_HK
dc.identifier.emailSham, MH: mhsham@hkucc.hku.hken_HK
dc.identifier.emailLui, VCH: vchlui@hkucc.hku.hken_HK
dc.identifier.emailTam, PKH: paultam@hkucc.hku.hken_HK
dc.identifier.authorityGarciaBarceló, M=rp00445en_HK
dc.identifier.authoritySham, MH=rp00380en_HK
dc.identifier.authorityLui, VCH=rp00363en_HK
dc.identifier.authorityTam, PKH=rp00060en_HK
dc.description.naturepublished_or_final_versionen_HK
dc.identifier.doi10.1136/gut.52.4.563en_HK
dc.identifier.pmid12631670en_HK
dc.identifier.pmcidPMC1773584-
dc.identifier.scopuseid_2-s2.0-0345385015en_HK
dc.identifier.hkuros82748-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0345385015&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume52en_HK
dc.identifier.issue4en_HK
dc.identifier.spage563en_HK
dc.identifier.epage567en_HK
dc.identifier.isiWOS:000181828100022-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridGarciaBarceló, M=6701767303en_HK
dc.identifier.scopusauthoridSham, MH=7003729109en_HK
dc.identifier.scopusauthoridLui, VCH=7004231344en_HK
dc.identifier.scopusauthoridChen, BLS=7408607939en_HK
dc.identifier.scopusauthoridOtt, J=7202757548en_HK
dc.identifier.scopusauthoridTam, PKH=7202539421en_HK

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