TY - JOUR
T1 - Genetic obesity: Next-generation sequencing results of 1230 patients with obesity
T2 - next-generation sequencing results of 1230 patients with obesity
AU - Kleinendorst, Lotte
AU - Massink, Maarten P. G.
AU - Cooiman, Mellody I.
AU - Savas, Mesut
AU - van der Baan-Slootweg, Olga H.
AU - Roelants, Roosje J.
AU - Janssen, Ignace C. M.
AU - Meijers-Heijboer, Hanne J.
AU - Knoers, Nine V. A. M.
AU - Ploos van Amstel, Hans Kristian
AU - van Rossum, Elisabeth F. C.
AU - van den Akker, Erica L. T.
AU - van Haaften, Gijs
AU - van der Zwaag, Bert
AU - van Haelst, Mieke M.
PY - 2018/9
Y1 - 2018/9
N2 - 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/m 2; 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.
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/m 2; 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.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85052432798&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/29970488
U2 - https://doi.org/10.1136/jmedgenet-2018-105315
DO - https://doi.org/10.1136/jmedgenet-2018-105315
M3 - Article
C2 - 29970488
SN - 0022-2593
VL - 55
SP - 578
EP - 586
JO - Journal of Medical Genetics
JF - Journal of Medical Genetics
IS - 9
ER -