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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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D'Angelo, Carla Sustek [1] ; Varela, Monica Castro [1] ; Emilio de Castro, Claudia Irene [1] ; Otto, Paulo Alberto [1] ; Alvarez Perez, Ana Beatriz [2] ; Lourenco, Charles Marques [3] ; Kim, Chong Ae [4] ; Bertola, Debora Romeo [4] ; Kok, Fernando [5] ; Garcia-Alonso, Luis [2] ; Koiffmann, Celia Priszkulnik [1]
Número total de Autores: 11
Afiliação do(s) autor(es):
[1] 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 - Brazil
[2] Fed Univ Sao Paulo UNIFESP, Paulista Sch Med, Dept Morphol & Genet, Sao Paulo, SP - Brazil
[3] Univ Sao Paulo, FMRP, Fac Med, Clin Hosp Ribeirao Preto, Neurogenet Unit, Ribeirao Preto, SP - Brazil
[4] Univ Sao Paulo, Fac Med, Childrens Inst, Genet Unit, FMUSP, Sao Paulo, SP - Brazil
[5] Univ Sao Paulo, Fac Med, Dept Neurol, FMUSP, Sao Paulo, SP - Brazil
Número total de Afiliações: 5
Tipo de documento: Artigo Científico
Fonte: MOLECULAR CYTOGENETICS; v. 11, FEB 5 2018.
Citações Web of Science: 2
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); 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. (AU)

Processo FAPESP: 98/14254-2 - Centro de Estudos do Genoma Humano
Beneficiário:Mayana Zatz
Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
Processo FAPESP: 09/52523-1 - Obesidade sindrômica: pesquisa de genes e segmentos cromossômicos associados à obesidade, descrição de novas síndromes e da variabilidade fenotípica em síndromes reconhecidas
Beneficiário:Carla Sustek D'Angelo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado