Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands.
Department of Genetics, Universitair Medisch Centrum Utrecht, Utrecht, The Netherlands.
J Med Genet. 2018 Sep;55(9):578-586. doi: 10.1136/jmedgenet-2018-105315. Epub 2018 Jul 3.
Obesity is a global and severe health problem. Due to genetic heterogeneity, the identification of genetic defects in patients with obesity can be time consuming and costly. Therefore, we developed a custom diagnostic targeted next-generation sequencing (NGS)-based analysis to simultaneously identify mutations in 52 obesity-related genes. The aim of this study was to assess the diagnostic yield of this approach in patients with suspected genetic obesity.
DNA of 1230 patients with obesity (median BMI adults 43.6 kg/m; median body mass index-SD children +3.4 SD) was analysed in the genome diagnostics section of the Department of Genetics of the UMC Utrecht (The Netherlands) by targeted analysis of 52 obesity-related genes.
In 48 patients pathogenic mutations confirming the clinical diagnosis were detected. The majority of these were observed in the gene (18/48). In an additional 67 patients a probable pathogenic mutation was identified, necessitating further analysis to confirm the clinical relevance.
NGS-based gene panel analysis in patients with obesity led to a definitive diagnosis of a genetic obesity disorder in 3.9% of obese probands, and a possible diagnosis in an additional 5.4% of obese probands. The highest yield was achieved in a selected paediatric subgroup, establishing a definitive diagnosis in 12 out of 164 children with severe early onset obesity (7.3%). These findings give a realistic insight in the diagnostic yield of genetic testing for patients with obesity and could help these patients to receive (future) personalised treatment.
肥胖是一个全球性的严重健康问题。由于遗传异质性，确定肥胖患者的遗传缺陷可能既耗时又昂贵。因此，我们开发了一种定制的诊断靶向下一代测序（NGS）分析方法，以同时识别 52 个与肥胖相关的基因中的突变。本研究的目的是评估该方法在疑似遗传性肥胖患者中的诊断效果。
荷兰乌得勒支大学医学中心遗传学系的基因组诊断科对 1230 名肥胖患者（成人平均 BMI 为 43.6kg/m，儿童 BMI 平均+3.4SD）的 DNA 进行了分析，方法是对 52 个与肥胖相关的基因进行靶向分析。
在 48 名患者中检测到了确认临床诊断的致病性突变。其中大多数发生在 基因（18/48）中。在另外 67 名患者中发现了可能的致病性突变，需要进一步分析以确认其临床相关性。
对肥胖患者进行基于 NGS 的基因面板分析，确定了 3.9%的肥胖先证者存在遗传性肥胖疾病的明确诊断，另有 5.4%的肥胖先证者可能存在该疾病。在一个选定的儿科亚组中，检测效果最佳，在 164 名患有严重早发性肥胖的儿童中，有 12 名（7.3%）确定了明确诊断。这些发现为肥胖患者进行基因检测的诊断效果提供了现实的见解，并有助于这些患者接受（未来）的个性化治疗。
