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Conference Paper: Patterns and rates of exonic de novo mutations in sporadic Hirschsprung disease patients

TitlePatterns and rates of exonic de novo mutations in sporadic Hirschsprung disease patients
Authors
KeywordsHirschsprung disease
Exome sequencing
de novo
Issue Date2013
PublisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ejhg
Citation
The 2013 European Human Genetics Conference (ESHG 2013), Paris, France, 8-11 June 2013. In European Journal of Human Genetics, 2013, v. 21 suppl. 2, p. 44, abstract no. C16.1 How to Cite?
AbstractHirschsprung disease (HSCR, aganglionic megacolon; 1 in 5000 live births) is a disorder of the enteric nervous system (ENS) characterized by the absence of enteric neurons along a variable length of the intestine. HSCR most commonly presents sporadically, although it can be familial (5-20% of the patients). The sporadic form of the disorder is believed to be a genetically complex disease with both de novo and/or inherited genetic lesions. To assess the role of de novo mutations (DNM) in sporadic HSCR, we performed exome sequencing on 16 HSCR patients and their unaffected parents. Standard BWA/GATK pipeline was used to map the sequence reads to human reference genome 19 and call genomic variants for all 48 samples simultaneously. Exonic DNM mutations were identified using KGGSeq. DNM candidates were scrutinized using Integrative Genomics Viewer (IGV) and those variants deemed plausible were validated by Sanger sequencing. In total we confirmed 20 DNM mutations (17 SNVs, 3 Indels) in 16 genes. Five DNM were identified in RET (major HSCR gene). CCR2, COL6A3, MED26, NUP98, HMCN1 and DENND3 had DNM mutations and were found mutated in independent HSCR patients. Importantly, some of these genes are members of pathways involved in the development of the ENS and the encoded proteins interact with known key signaling molecules. The overall exonic DNM mutation rate is 1.25 per HSCR trio, with 10 out of 16 (62.5%) patients harboring ≥ 1 DNM mutations. Therefore, DNM mutations, as inherited mutations, contribute to the development of sporadic HSCR.
DescriptionD - Concurrent Sessions C16. Developmental syndromes: no. C16.1
WH Gui was selected as one of the candidates for the Young Investigator Awards
Persistent Identifierhttp://hdl.handle.net/10722/193646
ISSN
2015 Impact Factor: 4.58
2015 SCImago Journal Rankings: 2.077

 

DC FieldValueLanguage
dc.contributor.authorGui, Hen_US
dc.contributor.authorSchriemer, Den_US
dc.contributor.authorEggen, BJLen_US
dc.contributor.authorHofstra, RMWen_US
dc.contributor.authorvan Ijcken, Wen_US
dc.contributor.authorvan den Hout, Men_US
dc.contributor.authorGriseri, Pen_US
dc.contributor.authorMatera, Ien_US
dc.contributor.authorCeccherini, Ien_US
dc.contributor.authorPelet, Aen_US
dc.contributor.authorAmiel, Jen_US
dc.contributor.authorLyonnet, Sen_US
dc.contributor.authorGarcia-Barcelo, Men_US
dc.contributor.authorTam, PKHen_US
dc.contributor.authorRuiz-Ferrer, Men_US
dc.contributor.authorAntinolo, Gen_US
dc.contributor.authorBorrego, Sen_US
dc.contributor.authorBerrios, Cen_US
dc.contributor.authorChakravarti, Aen_US
dc.date.accessioned2014-01-20T05:12:43Z-
dc.date.available2014-01-20T05:12:43Z-
dc.date.issued2013en_US
dc.identifier.citationThe 2013 European Human Genetics Conference (ESHG 2013), Paris, France, 8-11 June 2013. In European Journal of Human Genetics, 2013, v. 21 suppl. 2, p. 44, abstract no. C16.1en_US
dc.identifier.issn1018-4813-
dc.identifier.urihttp://hdl.handle.net/10722/193646-
dc.descriptionD - Concurrent Sessions C16. Developmental syndromes: no. C16.1-
dc.descriptionWH Gui was selected as one of the candidates for the Young Investigator Awards-
dc.description.abstractHirschsprung disease (HSCR, aganglionic megacolon; 1 in 5000 live births) is a disorder of the enteric nervous system (ENS) characterized by the absence of enteric neurons along a variable length of the intestine. HSCR most commonly presents sporadically, although it can be familial (5-20% of the patients). The sporadic form of the disorder is believed to be a genetically complex disease with both de novo and/or inherited genetic lesions. To assess the role of de novo mutations (DNM) in sporadic HSCR, we performed exome sequencing on 16 HSCR patients and their unaffected parents. Standard BWA/GATK pipeline was used to map the sequence reads to human reference genome 19 and call genomic variants for all 48 samples simultaneously. Exonic DNM mutations were identified using KGGSeq. DNM candidates were scrutinized using Integrative Genomics Viewer (IGV) and those variants deemed plausible were validated by Sanger sequencing. In total we confirmed 20 DNM mutations (17 SNVs, 3 Indels) in 16 genes. Five DNM were identified in RET (major HSCR gene). CCR2, COL6A3, MED26, NUP98, HMCN1 and DENND3 had DNM mutations and were found mutated in independent HSCR patients. Importantly, some of these genes are members of pathways involved in the development of the ENS and the encoded proteins interact with known key signaling molecules. The overall exonic DNM mutation rate is 1.25 per HSCR trio, with 10 out of 16 (62.5%) patients harboring ≥ 1 DNM mutations. Therefore, DNM mutations, as inherited mutations, contribute to the development of sporadic HSCR.-
dc.languageengen_US
dc.publisherNature Publishing Group. The Journal's web site is located at http://www.nature.com/ejhg-
dc.relation.ispartofEuropean Journal of Human Geneticsen_US
dc.subjectHirschsprung disease-
dc.subjectExome sequencing-
dc.subjectde novo-
dc.titlePatterns and rates of exonic de novo mutations in sporadic Hirschsprung disease patientsen_US
dc.typeConference_Paperen_US
dc.identifier.emailGui, H: kuei1985@hku.hken_US
dc.identifier.emailGarcia-Barcelo, M: mmgarcia@hku.hken_US
dc.identifier.emailTam, PKH: paultam@hku.hken_US
dc.identifier.authorityGarcia-Barcelo, M=rp00445en_US
dc.identifier.authorityTam, PKH=rp00060en_US
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros217536en_US
dc.identifier.hkuros227335-
dc.identifier.volume21-
dc.identifier.issuesuppl. 2-
dc.identifier.spage44-
dc.identifier.epage44-
dc.publisher.placeUnited Kingdom-

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