Genetic obesity: next-generation sequencing results of 1230 patients with obesity

Lotte Kleinendorst, Maarten P G Massink, Mellody I Cooiman, Mesut Savas, Olga H van der Baan-Slootweg, Roosje J Roelants, Ignace C M Janssen, Hanne J Meijers-Heijboer, Nine V A M Knoers, Hans Kristian Ploos van Amstel, Elisabeth F C van Rossum, Erica L T van den Akker, Gijs van Haaften, Bert van der Zwaag, Mieke M van Haelst

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)578-586
Number of pages9
JournalJournal of Medical Genetics
Volume55
Issue number9
DOIs
Publication statusPublished - Sep 2018

Cite this

Kleinendorst, L., Massink, M. P. G., Cooiman, M. I., Savas, M., van der Baan-Slootweg, O. H., Roelants, R. J., ... van Haelst, M. M. (2018). Genetic obesity: next-generation sequencing results of 1230 patients with obesity. Journal of Medical Genetics, 55(9), 578-586. https://doi.org/10.1136/jmedgenet-2018-105315