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

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

Author D'Angelo, Carla Sustek Google Scholar
Varela, Monica Castro Google Scholar
Emilio de Castro, Claudia Irene Google Scholar
Otto, Paulo Alberto Google Scholar
Alvarez Perez, Ana Beatriz Autor UNIFESP Google Scholar
Lourenco, Charles Marques Google Scholar
Kim, Chong Ae Google Scholar
Bertola, Debora Romeo Google Scholar
Kok, Fernando Google Scholar
Garcia-Alonso, Luis Autor UNIFESP Google Scholar
Koiffmann, Celia Priszkulnik Google Scholar
Abstract 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)

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.
Keywords Chromosomal microarray analysis (CMA)
Copy number variations (CNVs)
Body mass index (BMI)
Intellectual and developmental disabilities (IDDs)
Prader-Willi syndrome (PWS)
Syndromic obesity
xmlui.dri2xhtml.METS-1.0.item-coverage London
Language English
Sponsor State of Sao Paulo Research Foundation, FAPESP
Centers for Research, Innovation and Diffusion, CEPID-FAPESP
National Council for Scientific and Technological Development, CNPq
Grant number FAPESP: 09/52523-1
CEPID-FAPESP: 1998/14254-2
National Council for Scientific and Technological Development, CNPq: 304381/2007-1
Date 2018
Published in Molecular Cytogenetics. London, v. 11, p. -, 2018.
ISSN 1755-8166 (Sherpa/Romeo, impact factor)
Publisher Biomed Central Ltd
Extent -
Origin http://dx.doi.org/10.1186/s13039-018-0363-7
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000424131800001
URI https://repositorio.unifesp.br/handle/11600/54142

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