ESPE Abstracts (2019) 92 P1-336

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1Medical Genetics Unit, Meyer Children's University Hospital, Florence, Italy. 2Medical Genetics Unit, Department of Clinical and Experimental Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy. 3. Medical Genetics Unit, Department of Clinical and Experimental Biomedical Sciences 'Mario Serio', University of Florence, Florence, Italy. 4Department of Science's Health, Anna Meyer Children's University Hospital, Florence, Italy, Florence, Italy. 5Department of Science's Health, Anna Meyer Children's University Hospital, Florence, Italy


Obesity, with its complications, emerges as a major contributor to the global health burden becoming pandemic. It's an extremely complex disorder resulting of interaction of biological, social and behavioural factors that cause increase in food intake and reduction in energy expenditure. Although few monogenic forms and indeed several susceptibility loci have been described, the molecular basis underlying early onset obesity remain largely unknown. GWAS revealed consistent association between SNPs with BMI and fat-mass, but cannot demonstrate the undoubted causality, and elucidating the culprit events continues to be challenging, especially when it's not known the way in which variants primarily act. To expand our knowledge, we performed WES in 30 strictly clinical classified Caucasian probands with severe early-onset obesity. We screened a set of 80 responsible/susceptibility genes for syndromic/monogenic forms, including ones belonging to pathways linked to obesity development. We identified potentially pathogenic variants in 75% of our cases. 5 cases presented a single variant in genes related to increase of BMI/WHR, 3 patients had variants in hypothalamic leptin-melacortin pathway, whereas remaining cases showing complex genetic background with mutations in 2/more genes. WES analysis results allowed us to plan a tailored treatment in patients with family history of diabetes, hepatic steatosis and severe obesity who presented pathogenic variant in SH2B1, leaded significant weight loss. The systematic discovery of rare variants in complex diseases suggests that the reverse-strategy is fruitful for assigning pathogenic effects of several genes simultaneously: the genotype-first approach will be able to identify clinically recognizable phenotypes.

Volume 92

58th Annual ESPE

Vienna, Austria
19 Sep 2019 - 21 Sep 2019

European Society for Paediatric Endocrinology 

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