1184 The Leptin Puzzle: Decoding Genes, Morbid Obesity, Sleep-Related Disorders and Its Influence

Introduction The role of early-onset obesity-related genetic predisposition and leptin receptor variants have been studied in previous studies. However, sleep-related disorders related to a genetic predisposition, leading to obesity, and how leptin could play a role in sleep-related disorders have been limited. In this study, we explore a case of how leptin receptor variants could play a role in the relationship between obesity and sleep-related disorders. Report of case(s) Case of a 17-year-old Hispanic female presented with a history of frequent snoring, gasping for air while sleeping, daytime sleepiness, sleep onset, maintenance difficulties, and limb movements at sleep. Polysomnography (PSG) was performed and later diagnosed with Obstructive Sleep Apnea (OSA). Respiratory disturbances were associated with oxygen desaturation down to a nadir of 68 % during sleep and a mean oxygen saturation of 91%, with an AHI of 22.7 events/hr. Additional genetic studies were performed to assess the causes of obesity, presenting with BBS9 heterozygous gene for a sequence variant defined as c.396GC, which is predicted to result in the amino acid substitution p.Gln132His. Furthermore, this patient is heterozygous in the LEPR gene for a sequence variant defined as c.658GA, which is predicted to result in the amino acid substitution p.Val220Ile, which has been reported in the heterozygous state in severe obesity, which increases leptin levels due to mutations in its receptor. Conclusion Leptin dysregulation has been associated with an increased predisposition to obesity, which could lead to sleep-related disorders, such as OSA. What is novel in our case is that our patient has an LEPR gene heterozygous variant, leading to an increase in leptin levels, a greater increase in metabolic dysregulation, and increased body weight, thus worsening her OSA. At the same time, research has shown that conditions such as OSA also increase leptin levels, which could worsen her OSA and prognosis. Further research is needed to assess LEPR and its role in OSA, especially in Hispanic populations, where research is limited. Support (if any)