Integrative Variation Analysis Reveals that a Complex Genotype May Specify Phenotype in Siblings with Syndromic Autism Spectrum Disorder

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dc.citation.issue1
dc.citation.volume12
dc.contributor.authorde Souza Reis, Viviane Neri
dc.contributor.authorKitajima, Joao Paulo
dc.contributor.authorTahira, Ana Carolina
dc.contributor.authorFeio-dos-Santos, Cecillia
dc.contributor.authorFock, Rodrigo Ambrosio [UNIFESP]
dc.contributor.authorGarcia Lisboa, Bianca Cristina
dc.contributor.authorSimoes, Sergio Nery
dc.contributor.authorKrepischi, Ana C. V.
dc.contributor.authorRosenberg, Carla
dc.contributor.authorLourenco, Naila Cristina
dc.contributor.authorPassos-Bueno, Maria Rita
dc.contributor.authorBrentani, Helena
dc.coverageSan Francisco
dc.date.accessioned2020-07-17T14:03:13Z
dc.date.available2020-07-17T14:03:13Z
dc.date.issued2017
dc.description.abstractIt has been proposed that copy number variations (CNVs) are associated with increased risk of autism spectrum disorder (ASD) and, in conjunction with other genetic changes, contribute to the heterogeneity of ASD phenotypes. Array comparative genomic hybridization (aCGH) and exome sequencing, together with systems genetics and network analyses, are being used as tools for the study of complex disorders of unknown etiology, especially those characterized by significant genetic and phenotypic heterogeneity. Therefore, to characterize the complex genotype-phenotype relationship, we performed aCGH and sequenced the exomes of two affected siblings with ASD symptoms, dysmorphic features, and intellectual disability, searching for de novo CNVs, as well as for de novo and rare inherited point variations D single nucleotide variants (SNVs) or small insertions and deletions (indels) D with probable functional impacts. With aCGH, we identified, in both siblings, a duplication in the 4p16.3 region and a deletion at 8p23.3, inherited by a paternal balanced translocation, t(4, 8) (p16en
dc.description.abstractp23). Exome variant analysis found a total of 316 variants, of which 102 were shared by both siblings, 128 were in the male sibling exome data, and 86 were in the female exome data. Our integrative network analysis showed that the siblings' shared translocation could explain their similar syndromic phenotype, including overgrowth, macrocephaly, and intellectual disability. However, exome data aggregate genes to those already connected from their translocation, which are important to the robustness of the network and contribute to the understanding of the broader spectrum of psychiatric symptoms. This study shows the importance of using an integrative approach to explore genotype-phenotype variability.en
dc.description.affiliationUniv Sao Paulo, Inst Psychiat, Sch Med, LIM23, Sao Paulo, Brazil
dc.description.affiliationMendel Anal Genom, Bioinformat, Sao Paulo, Brazil
dc.description.affiliationUniv Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo, Brazil
dc.description.affiliationFed Inst Espirito Santo, Dept Informat, Serra, Brazil
dc.description.affiliationUniv Sao Paulo, Inst Biosci, Dept Genet & Evolutionary Biol, Sao Paulo, Brazil
dc.description.affiliationUnifespUniv Fed Sao Paulo, Dept Morphol & Genet, Sao Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipFAPESP - Sao Paulo Research Foundation
dc.description.sponsorshipCAPES - Brazilian Federal Agency for the Support and Evaluation of Graduate Education
dc.description.sponsorshipIDFAPESP: 2011/04956-6
dc.description.sponsorshipIDFAPESP: 2011/14658-2
dc.description.sponsorshipIDCAPES: PROEX-33002010073P7
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1371/journal.pone.0170386
dc.identifier.citationPlos One. San Francisco, v. 12, n. 1, p. -, 2017.
dc.identifier.doi10.1371/journal.pone.0170386
dc.identifier.fileWOS000396160500036.pdf
dc.identifier.issn1932-6203
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/55234
dc.identifier.wosWOS:000396160500036
dc.language.isoeng
dc.publisherPublic Library Science
dc.relation.ispartofPlos One
dc.rightsinfo:eu-repo/semantics/openAccess
dc.titleIntegrative Variation Analysis Reveals that a Complex Genotype May Specify Phenotype in Siblings with Syndromic Autism Spectrum Disorderen
dc.typeinfo:eu-repo/semantics/article
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