RT Journal Article SR Electronic T1 Genetic obesity: next-generation sequencing results of 1230 patients with obesity JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 578 OP 586 DO 10.1136/jmedgenet-2018-105315 VO 55 IS 9 A1 Kleinendorst, Lotte A1 Massink, Maarten P G A1 Cooiman, Mellody I A1 Savas, Mesut A1 van der Baan-Slootweg, Olga H A1 Roelants, Roosje J A1 Janssen, Ignace C M A1 Meijers-Heijboer, Hanne J A1 Knoers, Nine V A M A1 Ploos van Amstel, Hans Kristian A1 van Rossum, Elisabeth F C A1 van den Akker, Erica L T A1 van Haaften, Gijs A1 van der Zwaag, Bert A1 van Haelst, Mieke M YR 2018 UL http://jmg.bmj.com/content/55/9/578.abstract AB Background 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.Methods DNA of 1230 patients with obesity (median BMI adults 43.6 kg/m2; 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.Results In 48 patients pathogenic mutations confirming the clinical diagnosis were detected. The majority of these were observed in the MC4R gene (18/48). In an additional 67 patients a probable pathogenic mutation was identified, necessitating further analysis to confirm the clinical relevance.Conclusions 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.