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
Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Human Genetics Laboratory, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, Brazil.
Front Endocrinol (Lausanne). 2025 Jan 17;15:1495534. doi: 10.3389/fendo.2024.1495534. eCollection 2024.
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.
The sample comprised 195 adults with severe obesity (BMI≥35kg/m) 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.
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 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.
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.
遗传性肥胖被认为是一种罕见疾病，影响高达10%的重度早发性肥胖患者。在过去几年中取得了重大进展；然而，大多数患者被误诊为多基因肥胖。因此，本研究旨在识别与肥胖相关的有害拷贝数变异（CNV）并探索临床表型。
样本包括195名重度肥胖成年人（BMI≥35kg/m），他们在儿童期或青少年期出现了这种表型。我们使用多重连接依赖探针扩增法[MLPA]和实时PCR研究CNV。采用染色体微阵列分析评估基因组改变的程度。
一名患者在16p11.2区域远端出现约206 kb的缺失，包含12个基因。与重度肥胖发展相关的基因是 这种改变在一名患有代谢综合征（MS）和高血压的男性患者中被发现。两名患者在16p11.2区域近端出现大片段缺失。一名患者出现约534 kb的缺失，缺失29个基因。这名女性患者患有高血压和支气管炎。另一名患者在16p11.2区域近端出现约598 kb的缺失，包括32个基因。这名女性患者表现出MS和中度暴饮暴食症。
我们的研究显示，来自巴西的重度肥胖患者在16p11.2区域存在三个基因组缺失。这些结果支持基因检测在识别可能从特定医学治疗、家庭遗传咨询和靶向治疗干预中受益的遗传性肥胖患者方面的临床实用性。
