Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity

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dc.citation.volume11
dc.contributor.authorD'Angelo, Carla Sustek
dc.contributor.authorVarela, Monica Castro
dc.contributor.authorEmilio de Castro, Claudia Irene
dc.contributor.authorOtto, Paulo Alberto
dc.contributor.authorAlvarez Perez, Ana Beatriz [UNIFESP]
dc.contributor.authorLourenco, Charles Marques
dc.contributor.authorKim, Chong Ae
dc.contributor.authorBertola, Debora Romeo
dc.contributor.authorKok, Fernando
dc.contributor.authorGarcia-Alonso, Luis [UNIFESP]
dc.contributor.authorKoiffmann, Celia Priszkulnik
dc.coverageLondon
dc.date.accessioned2020-07-08T13:09:41Z
dc.date.available2020-07-08T13:09:41Z
dc.date.issued2018
dc.description.abstractBackground: Syndromic obesity is an umbrella term used to describe cases where obesity occurs with additional phenotypes. It often arises as part of a distinct genetic syndrome with Prader-Willi syndrome being a classical example. These rare forms of obesity provide a unique source for identifying obesity-related genetic changes. Chromosomal microarray analysis (CMA) has allowed the characterization of new genetic forms of syndromic obesity, which are due to copy number variants (CNVs)en
dc.description.abstracthowever, CMA in large cohorts requires more study. The aim of this study was to characterize the CNVs detected by CMA in 279 patients with a syndromic obesity phenotype. Results: Pathogenic CNVs were detected in 61 patients (22%) and, among them, 35 had overlapping/recurrent CNVs. Genomic imbalance disorders known to cause syndromic obesity were found in 8.2% of cases, most commonly deletions of 1p36, 2q37 and 17p11.2 (5.4%), and we also detected deletions at 1p21.3, 2p25.3, 6q16, 9q34, 16p11.2 distal and proximal, as well as an unbalanced translocation resulting in duplication of the GNB3 gene responsible for a syndromic for of childhood obesity. Deletions of 9p terminal and 22q11.2 proximal/distal were found in 1% and 3% of cases, respectively. They thus emerge as being new putative obesity-susceptibility loci. We found additional CNVs in our study that overlapped with CNVs previously reported in cases of syndromic obesity, including a new case of 13q34 deletion (CHAMP1), bringing to 7 the number of patients in whom such defects have been described in association with obesity. Our findings implicate many genes previously associated with obesity (e.g. PTBP2, TMEM18, MYT1L, POU3F2, SIM1, SH2B1), and also identified other potentially relevant candidates including TAS1R3, ALOX5AP, and GAS6. Conclusion: Understanding the genetics of obesity has proven difficult, and considerable insight has been obtained from the study of genomic disorders with obesity associated as part of the phenotype. In our study, CNVs known to be causal for syndromic obesity were detected in 8.2% of patients, but we provide evidence for a genetic basis of obesity in as many as 14% of cases. Overall, our results underscore the genetic heterogeneity in syndromic forms of obesity, which imposes a substantial challenge for diagnosis.en
dc.description.affiliationUniv Sao Paulo, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CELL, Dept Genet & Evolutionary Biol, Rua Matao 277, BR-05508090 Sao Paulo, SP, Brazil
dc.description.affiliationFed Univ Sao Paulo UNIFESP, Paulista Sch Med, Dept Morphol & Genet, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, FMRP, Fac Med, Clin Hosp Ribeirao Preto,Neurogenet Unit, Ribeirao Preto, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Childrens Inst, Genet Unit,FMUSP, Sao Paulo, SP, Brazil
dc.description.affiliationUniv Sao Paulo, Fac Med, Dept Neurol, FMUSP, Sao Paulo, SP, Brazil
dc.description.affiliationUnifespFed Univ Sao Paulo UNIFESP, Paulista Sch Med, Dept Morphol & Genet, Sao Paulo, SP, Brazil
dc.description.provenanceMade available in DSpace on 2020-07-08T13:09:41Z (GMT). No. of bitstreams: 0 Previous issue date: 2018. Added 1 bitstream(s) on 2020-07-08T13:33:36Z : No. of bitstreams: 1 WOS000424131800001.pdf: 2718119 bytes, checksum: 8469aa46c45f1c39bc11ddaac2b694e4 (MD5)en
dc.description.sourceWeb of Science
dc.description.sponsorshipState of Sao Paulo Research Foundation, FAPESP
dc.description.sponsorshipCenters for Research, Innovation and Diffusion, CEPID-FAPESP
dc.description.sponsorshipNational Council for Scientific and Technological Development, CNPq
dc.description.sponsorshipIDFAPESP: 09/52523-1
dc.description.sponsorshipIDCEPID-FAPESP: 1998/14254-2
dc.description.sponsorshipIDNational Council for Scientific and Technological Development, CNPq: 304381/2007-1
dc.format.extent-
dc.identifierhttp://dx.doi.org/10.1186/s13039-018-0363-7
dc.identifier.citationMolecular Cytogenetics. London, v. 11, p. -, 2018.
dc.identifier.doi10.1186/s13039-018-0363-7
dc.identifier.fileWOS000424131800001.pdf
dc.identifier.issn1755-8166
dc.identifier.urihttps://repositorio.unifesp.br/handle/11600/54142
dc.identifier.wosWOS:000424131800001
dc.language.isoeng
dc.publisherBiomed Central Ltd
dc.relation.ispartofMolecular Cytogenetics
dc.rightsAcesso aberto
dc.subjectChromosomal microarray analysis (CMA)en
dc.subjectCopy number variations (CNVs)en
dc.subjectBody mass index (BMI)en
dc.subjectIntellectual and developmental disabilities (IDDs)en
dc.subjectPrader-Willi syndrome (PWS)en
dc.subjectSyndromic obesityen
dc.titleChromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesityen
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