AUTHOR=da Silva Assis Izadora Sthephanie , Salum Kaio Cezar Rodrigues , Felício Rafaela de Freitas Martins , Palhinha Lohanna , de Medeiros Abreu Gabriella , Silva Tamara , Mattos Fernanda Cristina Carvalho , Rosado Eliane Lopes , Zembrzuski Verônica Marques , Campos Junior Mario , Maya-Monteiro Clarissa Menezes , Cabello Pedro Hernán , Carneiro João Regis Ivar , Bozza Patrícia Torres , da Fonseca Ana Carolina Proença TITLE=Genomic deletions on 16p11.2 associated with severe obesity in Brazil JOURNAL=Frontiers in Endocrinology VOLUME=Volume 15 - 2024 YEAR=2025 URL=https://www.frontiersin.org/journals/endocrinology/articles/10.3389/fendo.2024.1495534 DOI=10.3389/fendo.2024.1495534 ISSN=1664-2392 ABSTRACT=Introduction

Genetic obesity is considered a rare disease, affecting up to 10% of patients with severe early-onset obesity. Over the past years, significant advances have been made; however, the majority of patients are misdiagnosed with polygenic obesity. Thus, this study aimed to identify deleterious copy number variations (CNVs) linked to obesity and explore the clinical phenotypes.

Method

The sample comprised 195 adults with severe obesity (BMI≥35kg/m2) who developed this phenotype during childhood or adolescence. We investigated the CNV using Multiplex Ligation-dependent Probe Amplification [MLPA] and real-time PCR. Chromosomal microarray analysis was used to assess the extent of genomic alterations.

Results

One patient showed a ~206 kb deletion in the distal of the 16p11.2 region, encompassing twelve genes. The gene linked to the development of severe obesity was SH2B1. This alteration was found in a male patient with metabolic syndrome (MS), and hypertension. Two patients exhibited a large deletion in the proximal of the 16p11.2 region. One patient showed a ~534 kb deletion without twenty-nine genes. This female patient had hypertension and bronchitis. The other patient presented a ~598 kb deletion of the proximal 16p11.2 region, including thirty-two genes. This female patient exhibited MS, and moderate binge-eating disorder.

Conclusion

Our study showed three genomic deletions at the 16p11.2 region in patients with severe obesity from Brazil. These results support the clinical utility of genetic testing to identify patients with the genetic form of obesity who may benefit from specific medical treatment, family genetic counseling, and targeted therapeutic intervention.