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Article: Detection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice

TitleDetection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practice
Authors
Issue Date2009
PublisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
Citation
Journal Of Medical Genetics, 2009, v. 46 n. 2, p. 123-131 How to Cite?
AbstractMicroarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. Methods: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. Results: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. Conclusions: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.
Persistent Identifierhttp://hdl.handle.net/10722/170412
ISSN
2015 Impact Factor: 5.65
2015 SCImago Journal Rankings: 3.820
References

 

DC FieldValueLanguage
dc.contributor.authorBruno, DLen_US
dc.contributor.authorGanesamoorthy, Den_US
dc.contributor.authorSchoumans, Jen_US
dc.contributor.authorBankier, Aen_US
dc.contributor.authorComan, Den_US
dc.contributor.authorDelatycki, Men_US
dc.contributor.authorGardner, RJMen_US
dc.contributor.authorHunter, Men_US
dc.contributor.authorJames, PAen_US
dc.contributor.authorKannu, Pen_US
dc.contributor.authorMcgillivray, Gen_US
dc.contributor.authorPachter, Nen_US
dc.contributor.authorPeters, Hen_US
dc.contributor.authorRieubland, Cen_US
dc.contributor.authorSavarirayan, Ren_US
dc.contributor.authorScheffer, IEen_US
dc.contributor.authorSheffield, Len_US
dc.contributor.authorTan, Ten_US
dc.contributor.authorWhite, SMen_US
dc.contributor.authorYeung, Aen_US
dc.contributor.authorBowman, Zen_US
dc.contributor.authorNgo, Cen_US
dc.contributor.authorChoy, KWen_US
dc.contributor.authorCacheux, Ven_US
dc.contributor.authorWong, Len_US
dc.contributor.authorAmor, DJen_US
dc.contributor.authorSlater, HRen_US
dc.date.accessioned2012-10-30T06:08:17Z-
dc.date.available2012-10-30T06:08:17Z-
dc.date.issued2009en_US
dc.identifier.citationJournal Of Medical Genetics, 2009, v. 46 n. 2, p. 123-131en_US
dc.identifier.issn0022-2593en_US
dc.identifier.urihttp://hdl.handle.net/10722/170412-
dc.description.abstractMicroarray genome analysis is realising its promise for improving detection of genetic abnormalities in individuals with mental retardation and congenital abnormality. Copy number variations (CNVs) are now readily detectable using a variety of platforms and a major challenge is the distinction of pathogenic from ubiquitous, benign polymorphic CNVs. The aim of this study was to investigate replacement of time consuming, locus specific testing for specific microdeletion and microduplication syndromes with microarray analysis, which theoretically should detect all known syndromes with CNV aetiologies as well as new ones. Methods: Genome wide copy number analysis was performed on 117 patients using Affymetrix 250K microarrays. Results: 434 CNVs (195 losses and 239 gains) were found, including 18 pathogenic CNVs and 9 identified as "potentially pathogenic". Almost all pathogenic CNVs were larger than 500 kb, significantly larger than the median size of all CNVs detected. Segmental regions of loss of heterozygosity larger than 5 Mb were found in 5 patients. Conclusions: Genome microarray analysis has improved diagnostic success in this group of patients. Several examples of recently discovered "new syndromes" were found suggesting they are more common than previously suspected and collectively are likely to be a major cause of mental retardation. The findings have several implications for clinical practice. The study revealed the potential to make genetic diagnoses that were not evident in the clinical presentation, with implications for pretest counselling and the consent process. The importance of contributing novel CNVs to high quality databases for genotype-phenotype analysis and review of guidelines for selection of individuals for microarray analysis is emphasised.en_US
dc.languageengen_US
dc.publisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/en_US
dc.relation.ispartofJournal of Medical Geneticsen_US
dc.subject.meshCytogenetic Analysisen_US
dc.subject.meshGene Dosageen_US
dc.subject.meshGene Expression Profilingen_US
dc.subject.meshGenetic Variationen_US
dc.subject.meshGenome, Humanen_US
dc.subject.meshHumansen_US
dc.subject.meshIntellectual Disability - Diagnosis - Geneticsen_US
dc.subject.meshLoss Of Heterozygosityen_US
dc.subject.meshMicroarray Analysisen_US
dc.subject.meshPolymorphism, Single Nucleotide - Geneticsen_US
dc.titleDetection of cryptic pathogenic copy number variations and constitutional loss of heterozygosity using high resolution SNP microarray analysis in 117 patients referred for cytogenetic analysis and impact on clinical practiceen_US
dc.typeArticleen_US
dc.identifier.emailTan, T:tanty@hku.hken_US
dc.identifier.authorityTan, T=rp01380en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1136/img.2008.062604en_US
dc.identifier.pmid19015223-
dc.identifier.scopuseid_2-s2.0-62149085882en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-62149085882&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume46en_US
dc.identifier.issue2en_US
dc.identifier.spage123en_US
dc.identifier.epage131en_US
dc.publisher.placeUnited Kingdomen_US
dc.identifier.scopusauthoridBruno, DL=8047757000en_US
dc.identifier.scopusauthoridGanesamoorthy, D=26430762500en_US
dc.identifier.scopusauthoridSchoumans, J=6602455812en_US
dc.identifier.scopusauthoridBankier, A=7101962228en_US
dc.identifier.scopusauthoridComan, D=16834669700en_US
dc.identifier.scopusauthoridDelatycki, M=7005228584en_US
dc.identifier.scopusauthoridGardner, RJM=7401523685en_US
dc.identifier.scopusauthoridHunter, M=23488969800en_US
dc.identifier.scopusauthoridJames, PA=26323309200en_US
dc.identifier.scopusauthoridKannu, P=12801822000en_US
dc.identifier.scopusauthoridMcGillivray, G=8985369800en_US
dc.identifier.scopusauthoridPachter, N=26323277300en_US
dc.identifier.scopusauthoridPeters, H=7202544685en_US
dc.identifier.scopusauthoridRieubland, C=6508131635en_US
dc.identifier.scopusauthoridSavarirayan, R=7003566196en_US
dc.identifier.scopusauthoridScheffer, IE=7006332397en_US
dc.identifier.scopusauthoridSheffield, L=7007077793en_US
dc.identifier.scopusauthoridTan, T=8567188100en_US
dc.identifier.scopusauthoridWhite, SM=35480530300en_US
dc.identifier.scopusauthoridYeung, A=25640301700en_US
dc.identifier.scopusauthoridBowman, Z=26323114100en_US
dc.identifier.scopusauthoridNgo, C=36817837700en_US
dc.identifier.scopusauthoridChoy, KW=7005477052en_US
dc.identifier.scopusauthoridCacheux, V=24390743500en_US
dc.identifier.scopusauthoridWong, L=7402092162en_US
dc.identifier.scopusauthoridAmor, DJ=7004097069en_US
dc.identifier.scopusauthoridSlater, HR=7006294268en_US

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