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Article: Phenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder

TitlePhenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorder
Authors
Issue Date2010
PublisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/
Citation
Journal Of Medical Genetics, 2010, v. 47 n. 3, p. 195-203 How to Cite?
AbstractBackground Recurrent microdeletions and microduplications of w555 kb at 16p11.2 confer susceptibility to autism spectrum disorder (ASD) in up to 1% of ASD patients. No physical or behavioural features have been identified that distinguish these individuals as having a distinct ASD subtype, but clinical data are limited. Methods We report five autistic probands identified by microarray analysis with copy number variation (CNV) of 16p11.2 (three deletions, two duplications). Each patient was assessed for ASD and dysmorphic features. We also describe a deletion positive 26-month-old female who has developmental delay (DD) and autistic features. Results Proband 1 (female with ASD, de novo deletion) is not dysmorphic. Proband 2 (male with autism, de novo deletion) and proband 3 and his brother (males with autism, inherited deletions) are dysmorphic, but the two probands do not resemble one another. The mother of proband 3 has mild mental retardation (MR), minor dysmorphism and meets the criteria for ASD. Proband 4 (dysmorphic autistic male, de novo duplication) had a congenital diaphragmatic hernia. Proband 5 (nondysmorphic ASD female with a duplication) has two apparently healthy duplication positive relatives. Probands 1 and 2 have deletion negative siblings with ASD and Asperger syndrome, respectively. Proband 6 (a female with DD and an inherited duplication) is dysmorphic, but has oligohydramnios sequence. Conclusions The phenotypic spectrum associated with CNV at 16p11.2 includes ASD, MR/DD and/or possibly other primary psychiatric disorders. Compared with the microduplications, the reciprocal microdeletions are more likely to be penetrant and to be associated with nonspecific major or minor dysmorphism. There are deletion positive ASD probands with a less severe phenotype than deletion negative ASD siblings underscoring the significant phenotypic heterogeneity.
Persistent Identifierhttp://hdl.handle.net/10722/123851
ISSN
2015 Impact Factor: 5.65
2015 SCImago Journal Rankings: 3.820
ISI Accession Number ID
Funding AgencyGrant Number
Genome Canada/Ontario Genomics Institute
Canadian Institutes of Health Research (CIHR)
McLaughlin Centre for Molecular Medicine
Canadian Institute of Advanced Research
McMaster Children's Hospital Foundation
Hospital for Sick Children (SickKids) Foundation
SickKids Foundation
National Alliance for Research on Schizophrenia and Depression (NARSAD)
Funding Information:

Genome Canada/Ontario Genomics Institute, the Canadian Institutes of Health Research (CIHR), the McLaughlin Centre for Molecular Medicine, the Canadian Institute of Advanced Research, Autism Speaks, the McMaster Children's Hospital Foundation and the Hospital for Sick Children (SickKids) Foundation. CRM is supported by the SickKids Foundation and the National Alliance for Research on Schizophrenia and Depression (NARSAD). SWS holds the GlaxoSmithKline-CIHR Pathfinder Chair in Genetics and Genomics at the University of Toronto and Hospital for Sick Children.

References

 

DC FieldValueLanguage
dc.contributor.authorFernandez, BAen_HK
dc.contributor.authorRoberts, Wen_HK
dc.contributor.authorChung, Ben_HK
dc.contributor.authorWeksberg, Ren_HK
dc.contributor.authorMeyn, Sen_HK
dc.contributor.authorSzatmari, Pen_HK
dc.contributor.authorJosephGeorge, AMen_HK
dc.contributor.authorMacKay, Sen_HK
dc.contributor.authorWhitten, Ken_HK
dc.contributor.authorNoble, Ben_HK
dc.contributor.authorVardy, Cen_HK
dc.contributor.authorCrosbie, Ven_HK
dc.contributor.authorLuscombe, Sen_HK
dc.contributor.authorTucker, Een_HK
dc.contributor.authorTurner, Len_HK
dc.contributor.authorMarshall, CRen_HK
dc.contributor.authorScherer, SWen_HK
dc.date.accessioned2010-10-05T01:37:36Z-
dc.date.available2010-10-05T01:37:36Z-
dc.date.issued2010en_HK
dc.identifier.citationJournal Of Medical Genetics, 2010, v. 47 n. 3, p. 195-203en_HK
dc.identifier.issn0022-2593en_HK
dc.identifier.urihttp://hdl.handle.net/10722/123851-
dc.description.abstractBackground Recurrent microdeletions and microduplications of w555 kb at 16p11.2 confer susceptibility to autism spectrum disorder (ASD) in up to 1% of ASD patients. No physical or behavioural features have been identified that distinguish these individuals as having a distinct ASD subtype, but clinical data are limited. Methods We report five autistic probands identified by microarray analysis with copy number variation (CNV) of 16p11.2 (three deletions, two duplications). Each patient was assessed for ASD and dysmorphic features. We also describe a deletion positive 26-month-old female who has developmental delay (DD) and autistic features. Results Proband 1 (female with ASD, de novo deletion) is not dysmorphic. Proband 2 (male with autism, de novo deletion) and proband 3 and his brother (males with autism, inherited deletions) are dysmorphic, but the two probands do not resemble one another. The mother of proband 3 has mild mental retardation (MR), minor dysmorphism and meets the criteria for ASD. Proband 4 (dysmorphic autistic male, de novo duplication) had a congenital diaphragmatic hernia. Proband 5 (nondysmorphic ASD female with a duplication) has two apparently healthy duplication positive relatives. Probands 1 and 2 have deletion negative siblings with ASD and Asperger syndrome, respectively. Proband 6 (a female with DD and an inherited duplication) is dysmorphic, but has oligohydramnios sequence. Conclusions The phenotypic spectrum associated with CNV at 16p11.2 includes ASD, MR/DD and/or possibly other primary psychiatric disorders. Compared with the microduplications, the reciprocal microdeletions are more likely to be penetrant and to be associated with nonspecific major or minor dysmorphism. There are deletion positive ASD probands with a less severe phenotype than deletion negative ASD siblings underscoring the significant phenotypic heterogeneity.en_HK
dc.languageeng-
dc.publisherBMJ Group. The Journal's web site is located at http://jmg.bmj.com/en_HK
dc.relation.ispartofJournal of Medical Geneticsen_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subject.meshAdolescent-
dc.subject.meshChild Development Disorders, Pervasive - diagnosis - genetics-
dc.subject.meshChromosomes, Human, Pair 16-
dc.subject.meshGene Deletion-
dc.subject.meshGene Duplication-
dc.titlePhenotypic spectrum associated with de novo and inherited deletions and duplications at 16p11.2 in individuals ascertained for diagnosis of autism spectrum disorderen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0022-2593&volume=47&issue=3&spage=195&epage=203&date=2010&atitle=Phenotypic+spectrum+associated+with+de+novo+and+inherited+deletions+and+duplications+at+16p11.2+in+individuals+ascertained+for+diagnosis+of+autism+spectrum+disorder-
dc.identifier.emailChung, B:bhychung@hku.hken_HK
dc.identifier.authorityChung, B=rp00473en_HK
dc.description.naturepublished_or_final_version-
dc.identifier.doi10.1136/jmg.2009.069369en_HK
dc.identifier.pmid19755429-
dc.identifier.scopuseid_2-s2.0-77949718910en_HK
dc.identifier.hkuros170369-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-77949718910&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume47en_HK
dc.identifier.issue3en_HK
dc.identifier.spage195en_HK
dc.identifier.epage203en_HK
dc.identifier.eissn1468-6244-
dc.identifier.isiWOS:000275771600009-
dc.publisher.placeUnited Kingdomen_HK
dc.identifier.scopusauthoridFernandez, BA=7201505098en_HK
dc.identifier.scopusauthoridRoberts, W=7403316556en_HK
dc.identifier.scopusauthoridChung, B=7203043997en_HK
dc.identifier.scopusauthoridWeksberg, R=7006112330en_HK
dc.identifier.scopusauthoridMeyn, S=8711460000en_HK
dc.identifier.scopusauthoridSzatmari, P=7006673362en_HK
dc.identifier.scopusauthoridJosephGeorge, AM=8911109200en_HK
dc.identifier.scopusauthoridMacKay, S=36151106100en_HK
dc.identifier.scopusauthoridWhitten, K=36945815200en_HK
dc.identifier.scopusauthoridNoble, B=36151036200en_HK
dc.identifier.scopusauthoridVardy, C=23394162600en_HK
dc.identifier.scopusauthoridCrosbie, V=23391706100en_HK
dc.identifier.scopusauthoridLuscombe, S=23392947100en_HK
dc.identifier.scopusauthoridTucker, E=36151522600en_HK
dc.identifier.scopusauthoridTurner, L=36935248900en_HK
dc.identifier.scopusauthoridMarshall, CR=7201903397en_HK
dc.identifier.scopusauthoridScherer, SW=35374654500en_HK

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