Obesity is a major global health issue with multifactorial etiologies. Among them, recent advances in the comprehension of eating and energy regulation showed that around 60 genes involved in the hypo Show more
Obesity is a major global health issue with multifactorial etiologies. Among them, recent advances in the comprehension of eating and energy regulation showed that around 60 genes involved in the hypothalamic leptin/melanocortin pathway contribute to the development of rare monogenic or syndromic forms of obesity. To better delineate the genetic diagnostic rate and the phenotype in a cohort of early onset obesity and to integrate our results in guidance for genetic testing. In a diagnostic setting, 223 patients with early onset obesity were screened through a targeted panel including 44 genes for severe early onset obesity. Genetic results and clinical descriptions were reviewed for the entire cohort. A diagnostic yield of 3.1% was established. Likely pathogenic or pathogenic variants were found in Our work found a diagnostic yield of 3.1%. Additionally, 19.7% of heterozygous variants of unknown significance were found in genes related to autosomal conditions and 34.9% in genes related to recessive conditions. These results highlight the need for accurate genotype-phenotype correlations. Genetic laboratory expertise in obesity is highly recommended, especially in the context of the availability of new targeted anti-obesity therapies that open the field for current and future perspectives of these targeted genetic investigations. Show less