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

Detalhes bibliográficos
Autor(a) principal: D'Angelo, Carla Sustek
Data de Publicação: 2018
Outros Autores: Varela, Monica Castro, Emilio de Castro, Claudia Irene, Otto, Paulo Alberto, Alvarez Perez, Ana Beatriz [UNIFESP], Lourenco, Charles Marques, Kim, Chong Ae, Bertola, Debora Romeo, Kok, Fernando, Garcia-Alonso, Luis [UNIFESP], Koiffmann, Celia Priszkulnik
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNIFESP
Texto Completo: http://dx.doi.org/10.1186/s13039-018-0363-7
https://repositorio.unifesp.br/handle/11600/54142
Resumo: Background: 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)
id UFSP_3f440d9b24d1458d181e7700446f1f53
oai_identifier_str oai:repositorio.unifesp.br/:11600/54142
network_acronym_str UFSP
network_name_str Repositório Institucional da UNIFESP
repository_id_str 3465
spelling Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesityChromosomal microarray analysis (CMA)Copy number variations (CNVs)Body mass index (BMI)Intellectual and developmental disabilities (IDDs)Prader-Willi syndrome (PWS)Syndromic obesityBackground: 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)however, 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.Univ Sao Paulo, Inst Biosci, Human Genome & Stem Cell Res Ctr HUG CELL, Dept Genet & Evolutionary Biol, Rua Matao 277, BR-05508090 Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Paulista Sch Med, Dept Morphol & Genet, Sao Paulo, SP, BrazilUniv Sao Paulo, FMRP, Fac Med, Clin Hosp Ribeirao Preto,Neurogenet Unit, Ribeirao Preto, SP, BrazilUniv Sao Paulo, Fac Med, Childrens Inst, Genet Unit,FMUSP, Sao Paulo, SP, BrazilUniv Sao Paulo, Fac Med, Dept Neurol, FMUSP, Sao Paulo, SP, BrazilFed Univ Sao Paulo UNIFESP, Paulista Sch Med, Dept Morphol & Genet, Sao Paulo, SP, BrazilWeb of ScienceState of Sao Paulo Research Foundation, FAPESPCenters for Research, Innovation and Diffusion, CEPID-FAPESPNational Council for Scientific and Technological Development, CNPqFAPESP: 09/52523-1CEPID-FAPESP: 1998/14254-2National Council for Scientific and Technological Development, CNPq: 304381/2007-1Biomed Central Ltd2020-07-08T13:09:41Z2020-07-08T13:09:41Z2018info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersion-application/pdfhttp://dx.doi.org/10.1186/s13039-018-0363-7Molecular Cytogenetics. London, v. 11, p. -, 2018.10.1186/s13039-018-0363-7WOS000424131800001.pdf1755-8166https://repositorio.unifesp.br/handle/11600/54142WOS:000424131800001engMolecular CytogeneticsLondoninfo:eu-repo/semantics/openAccessD'Angelo, Carla SustekVarela, Monica CastroEmilio de Castro, Claudia IreneOtto, Paulo AlbertoAlvarez Perez, Ana Beatriz [UNIFESP]Lourenco, Charles MarquesKim, Chong AeBertola, Debora RomeoKok, FernandoGarcia-Alonso, Luis [UNIFESP]Koiffmann, Celia Priszkulnikreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESP2024-08-03T06:34:21Zoai:repositorio.unifesp.br/:11600/54142Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestbiblioteca.csp@unifesp.bropendoar:34652024-08-03T06:34:21Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false
dc.title.none.fl_str_mv Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
title Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
spellingShingle Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
D'Angelo, Carla Sustek
Chromosomal microarray analysis (CMA)
Copy number variations (CNVs)
Body mass index (BMI)
Intellectual and developmental disabilities (IDDs)
Prader-Willi syndrome (PWS)
Syndromic obesity
title_short Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
title_full Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
title_fullStr Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
title_full_unstemmed Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
title_sort Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
author D'Angelo, Carla Sustek
author_facet D'Angelo, Carla Sustek
Varela, Monica Castro
Emilio de Castro, Claudia Irene
Otto, Paulo Alberto
Alvarez Perez, Ana Beatriz [UNIFESP]
Lourenco, Charles Marques
Kim, Chong Ae
Bertola, Debora Romeo
Kok, Fernando
Garcia-Alonso, Luis [UNIFESP]
Koiffmann, Celia Priszkulnik
author_role author
author2 Varela, Monica Castro
Emilio de Castro, Claudia Irene
Otto, Paulo Alberto
Alvarez Perez, Ana Beatriz [UNIFESP]
Lourenco, Charles Marques
Kim, Chong Ae
Bertola, Debora Romeo
Kok, Fernando
Garcia-Alonso, Luis [UNIFESP]
Koiffmann, Celia Priszkulnik
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv D'Angelo, Carla Sustek
Varela, Monica Castro
Emilio de Castro, Claudia Irene
Otto, Paulo Alberto
Alvarez Perez, Ana Beatriz [UNIFESP]
Lourenco, Charles Marques
Kim, Chong Ae
Bertola, Debora Romeo
Kok, Fernando
Garcia-Alonso, Luis [UNIFESP]
Koiffmann, Celia Priszkulnik
dc.subject.por.fl_str_mv Chromosomal microarray analysis (CMA)
Copy number variations (CNVs)
Body mass index (BMI)
Intellectual and developmental disabilities (IDDs)
Prader-Willi syndrome (PWS)
Syndromic obesity
topic Chromosomal microarray analysis (CMA)
Copy number variations (CNVs)
Body mass index (BMI)
Intellectual and developmental disabilities (IDDs)
Prader-Willi syndrome (PWS)
Syndromic obesity
description Background: 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)
publishDate 2018
dc.date.none.fl_str_mv 2018
2020-07-08T13:09:41Z
2020-07-08T13:09:41Z
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1186/s13039-018-0363-7
Molecular Cytogenetics. London, v. 11, p. -, 2018.
10.1186/s13039-018-0363-7
WOS000424131800001.pdf
1755-8166
https://repositorio.unifesp.br/handle/11600/54142
WOS:000424131800001
url http://dx.doi.org/10.1186/s13039-018-0363-7
https://repositorio.unifesp.br/handle/11600/54142
identifier_str_mv Molecular Cytogenetics. London, v. 11, p. -, 2018.
10.1186/s13039-018-0363-7
WOS000424131800001.pdf
1755-8166
WOS:000424131800001
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Molecular Cytogenetics
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv -
application/pdf
dc.coverage.none.fl_str_mv London
dc.publisher.none.fl_str_mv Biomed Central Ltd
publisher.none.fl_str_mv Biomed Central Ltd
dc.source.none.fl_str_mv reponame:Repositório Institucional da UNIFESP
instname:Universidade Federal de São Paulo (UNIFESP)
instacron:UNIFESP
instname_str Universidade Federal de São Paulo (UNIFESP)
instacron_str UNIFESP
institution UNIFESP
reponame_str Repositório Institucional da UNIFESP
collection Repositório Institucional da UNIFESP
repository.name.fl_str_mv Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)
repository.mail.fl_str_mv biblioteca.csp@unifesp.br
_version_ 1814268296552251392

Registros relacionados