ESPE Abstracts

Genetic obesity is rare and usually affects the hunger/satiety circuit. Monogenic obesity is mainly due to variants in genes of the leptin-melanocortin pathway which regulates the control of food intake. Melanocortin 4 receptor (MC4R)-linked obesity has been reported as one of the most common forms of monogenic obesity. Mutations in the MC4R gene have been described in 2-3% of obese children and adults with variable severity of obesity and no additional phenotype. Syndromic ob...

Background/Objectives: Obesity poses a major public health concern. Although studies estimate that the heritability of BMI lies around 40–50%, the underlying genetics are still poorly understood. In monogenic obesity, solitary genetic variations significantly increase obesity risk. We therefore aim to (1) report the diagnostic yield of monogenic obesity using exome-wide data in a large cohort of over 500 individuals and aim to (2) improve future diagnost...

Background: We have identified a novel tandem duplication leading to ubiquitous expression of the agouti-signaling protein (ASIP) in a female patient with severe early onset obesity, red hair, tall stature, and insulin resistance (Kempf, E. et al, 2022). Due to the ectopic expression, ASIP - which normally is only expressed in the skin - can interact with the Melanocortin-4-Receptor receptor in the hypothalamus thereby causing the obesity phenotype. <p cla...

Background: GNAS (Guanine Nucleotide-Binding Protein, Alpha Stimulating) is an imprinted gene that encodes the alpha subunit of the stimulatory G protein (Gsa), which mediates the signaling of various G protein-coupled receptors. Inactivating genetic and epigenetic changes in GNAS, leading to Gsa deficiency, are associated with different subtypes of pseudohypoparathyroidism, which may include severe, early-onset obesity ...

Introduction and aims: The GRB10 gene codes for an adaptor protein that potentiates leptin signaling but inhibits IGF-I and insulin signaling. It is located on chromosome 7 and is imprinted in an isoform- and tissue-specific manner. The role of GRB10 in postnatal growth and obesity is not well understood, despite the fact that two imprinted disorders, Silver-Russell and Beckwith-Wiedmann syndromes, with distinctive postnatal growth abnormalit...

Introduction: A global methylation array previously performed by our group in placental samples revealed a nominal association of a CpG site (CpGs) located at chr14:104552209 in the ASPG (Asparaginase) gene with childhood obesity. ASPG (Asparaginase) when used to treat haematologic neoplasms can cause liver steatosis. Asparaginase reduces asparagine blood levels, which is known to promote the development of metabolic syndrome and obesity in both child...