Genetic obesity:next-generation sequencing results of 1230 patients with obesity
| Autor: | Hanne Meijers-Heijboer, Olga H van der Baan-Slootweg, Maarten P.G. Massink, Gijs van Haaften, Bert van der Zwaag, Mesut Savas, Elisabeth F.C. van Rossum, Nine V A M Knoers, Mellody I. Cooiman, Mieke M. van Haelst, Lotte Kleinendorst, Hans Kristian Ploos van Amstel, Ignace C M Janssen, Roosje J Roelants, Erica L T van den Akker |
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| Přispěvatelé: | VU University medical center, Human genetics, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Reproduction & Development (AR&D), ARD - Amsterdam Reproduction and Development, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, ACS - Atherosclerosis & ischemic syndromes, ACS - Diabetes & metabolism, Human Genetics, Internal Medicine, Pediatrics |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
Male
0301 basic medicine Proband SURGERY MELANOCORTIN-4 RECEPTOR leptin-melanocortin pathway MC4R medicine.disease_cause Body Mass Index 0302 clinical medicine Weight loss Genetics(clinical) Child Genetics (clinical) Netherlands Mutation medicine.diagnostic_test High-Throughput Nucleotide Sequencing POMC Middle Aged Pedigree MORBID-OBESITY LEPR Child Preschool Female Median body medicine.symptom Adult medicine.medical_specialty Adolescent WEIGHT-LOSS 030209 endocrinology & metabolism diagnostics tests EARLY-ONSET OBESITY Genetic Heterogeneity Young Adult endocrinology genetic obesity 03 medical and health sciences SDG 3 - Good Health and Well-being Internal medicine Genetics medicine Humans Genetic Predisposition to Disease Clinical significance Genetic Testing Obesity Aged Genetic testing Polymorphism Genetic Genetic heterogeneity business.industry Infant Newborn Infant Sequence Analysis DNA medicine.disease 030104 developmental biology business |
| Zdroj: | Kleinendorst, L, Massink, M P G, Cooiman, M I, Savas, M, van der Baan-Slootweg, O H, Roelants, R J, Janssen, I C M, Meijers-Heijboer, H J, Knoers, N V A M, Ploos van Amstel, H K, van Rossum, E F C, van den Akker, E L T, van Haaften, G, van der Zwaag, B & van Haelst, M M 2018, ' Genetic obesity : next-generation sequencing results of 1230 patients with obesity ', Journal of Medical Genetics, vol. 55, no. 9, pp. 578-586 . https://doi.org/10.1136/jmedgenet-2018-105315 Journal of Medical Genetics, 55(9), 578. BMJ Publishing Group Journal of Medical Genetics, 55(9), 578-586. BMJ Publishing Group JOURNAL OF MEDICAL GENETICS, 55(9), 578-586. BMJ PUBLISHING GROUP Journal of medical genetics, 55(9), 578-586. BMJ Publishing Group |
| ISSN: | 0022-2593 |
| DOI: | 10.1136/jmedgenet-2018-105315 |
| Popis: | BackgroundObesity 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.MethodsDNA 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.ResultsIn 48 patients pathogenic mutations confirming the clinical diagnosis were detected. The majority of these were observed in theMC4Rgene (18/48). In an additional 67 patients a probable pathogenic mutation was identified, necessitating further analysis to confirm the clinical relevance.ConclusionsNGS-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. |
| Databáze: | OpenAIRE |
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