Chromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesity
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2018 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da UNIFESP |
| Texto Completo: | https://repositorio.unifesp.br/handle/11600/54142 http://dx.doi.org/10.1186/s13039-018-0363-7 |
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) |
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D'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 Priszkulnik2020-07-08T13:09:41Z2020-07-08T13:09:41Z2018Molecular Cytogenetics. London, v. 11, p. -, 2018.1755-8166https://repositorio.unifesp.br/handle/11600/54142http://dx.doi.org/10.1186/s13039-018-0363-7WOS000424131800001.pdf10.1186/s13039-018-0363-7WOS:000424131800001Background: 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.State of Sao Paulo Research Foundation, FAPESPCenters for Research, Innovation and Diffusion, CEPID-FAPESPNational Council for Scientific and Technological Development, CNPqUniv 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, BrazilFAPESP: 09/52523-1CEPID-FAPESP: 1998/14254-2National Council for Scientific and Technological Development, CNPq: 304381/2007-1Web of Science-engBiomed Central LtdMolecular CytogeneticsChromosomal microarray analysis (CMA)Copy number variations (CNVs)Body mass index (BMI)Intellectual and developmental disabilities (IDDs)Prader-Willi syndrome (PWS)Syndromic obesityChromosomal microarray analysis in the genetic evaluation of 279 patients with syndromic obesityinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleLondon11info:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000424131800001.pdfapplication/pdf2718119${dspace.ui.url}/bitstream/11600/54142/1/WOS000424131800001.pdf8469aa46c45f1c39bc11ddaac2b694e4MD51open accessTEXTWOS000424131800001.pdf.txtWOS000424131800001.pdf.txtExtracted texttext/plain76202${dspace.ui.url}/bitstream/11600/54142/2/WOS000424131800001.pdf.txta8513efe6d137f5052da451e39061fe5MD52open accessTHUMBNAILWOS000424131800001.pdf.jpgWOS000424131800001.pdf.jpgIM Thumbnailimage/jpeg6598${dspace.ui.url}/bitstream/11600/54142/4/WOS000424131800001.pdf.jpg61db6092233d8ccc2c13621b1e88dc5fMD54open access11600/541422022-08-01 07:57:46.405open accessoai:repositorio.unifesp.br:11600/54142Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652022-08-01T10:57:46Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
| dc.title.en.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.eng.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) |
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2018 |
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2018 |
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2020-07-08T13:09:41Z |
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2020-07-08T13:09:41Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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Molecular Cytogenetics. London, v. 11, p. -, 2018. |
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https://repositorio.unifesp.br/handle/11600/54142 http://dx.doi.org/10.1186/s13039-018-0363-7 |
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1755-8166 |
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WOS000424131800001.pdf |
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10.1186/s13039-018-0363-7 |
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WOS:000424131800001 |
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Molecular Cytogenetics. London, v. 11, p. -, 2018. 1755-8166 WOS000424131800001.pdf 10.1186/s13039-018-0363-7 WOS:000424131800001 |
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https://repositorio.unifesp.br/handle/11600/54142 http://dx.doi.org/10.1186/s13039-018-0363-7 |
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eng |
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Molecular Cytogenetics |
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London |
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Biomed Central Ltd |
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Biomed Central Ltd |
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