hrp0095p1-79 | Fat, Metabolism and Obesity | ESPE2022

Severe early-onset obesity and diabetic ketoacidosis due to a novel homozygous c.169C>T p.Arg57* mutation in CEP19 gene

Cayir Atilla , Turkyilmaz Ayberk , Rabenstein Hannah , Guven Fadime , Sumeyra Karagoz Yuksel , Wabitsch Martin , Demirbilek Huseyin

Background and Objective: Homozygous mutations in the “Centrosomal Protein-19 (CEP19)” gene are extremely rare causes of early-onset severe monogenic obesity. We, herein, report three siblings with CEP19 mutation.Case Presentation and Method: The index case was a 12-years-old female who presented with severe obesity (BMI:62.7kg/m2), metabolic syndrome and diabetic ketoacidosis. Her non-identical twin female s...

hrp0094p1-120 | Fat, Metabolism and Obesity B | ESPE2021

Monogenic obesity in children: focusing on SH2B1 deletion

Giannopoulou Eleni Z , Zorn Stefanie , Schirmer Melanie , Herrmann Gloria , Heger Sabine , Reinehr Thomas , Denzer Christian , Rabenstein Hannah , Schnurbein Julia von , Wabitsch Martin ,

Introduction: Monogenic obesity refers to a group of rare, early-onset forms of obesity and accounts for about 7% of patients with severe pediatric obesity. Recent reports demonstrate the emerging role of Src-homology-2 (SH2) B adaptor protein 1 (Sh2b1), an important component in the leptin-melanocortin pathway, as a key regulator of leptin and insulin signaling, with possible roles in the pathogenesis of obesity and diabetes. SH2B1 deletions are found to be a...

hrp0092p1-51 | Fat, Metabolism and Obesity | ESPE2019

Pathogenic Mutations and Variants in KSR2 in a Cohort of Obese Children

Körber Ingrid , Sowada Nadine , Schirmer Melanie , Herrmann Gloria , Nunziata Adriana , Bald Martin , Ehehalt Stefan , Paetow Ulrich , Ohlenschläger Ute , Rabenstein Hannah , Siebert Reiner , von Schnurbein Julia , Wabitsch Martin

Background: Kinase suppressor of Ras 2 (KSR2) gene codes for a scaffold protein modulating intracellular pathways that involve MEK/BRAF cascade and AMPK signaling. KSR2 plays an important role in energy balance regulation, and KSR2 mutations were reported to be associated with obesity and insulin resistance in mice and humans. In transfected cells, several KSR2 mutations lead to impaired fatty acid oxidation, which improved under met...