![]() ![]() A Boy with a Novel Mutation in the Leptin Gene. Here we describe a case of early-onset extreme obesity due to a novel mutation in the leptin gene, accompanied by production and secretion of a mutant protein that is biologically inactive. 14 Whether such congenital leptin dysfunction could also occur in humans has been unclear. 14 The affected animals have hyperphagia and extreme obesity but also have marked hyperleptinemia, which suggests that the mutant leptin is biologically inactive. 9 However, a novel mutation in the murine gene encoding leptin (p.V145E) was generated by means of N-ethyl- N-nitrosourea mutagenesis. 2,3,5-8 Likewise, the corresponding ob/ob mouse model lacks leptin in the circulation. To date, reported cases of congenital leptin deficiency have been characterized by circulating leptin levels that are undetectable or very low as a result of defects in either synthesis or secretion of leptin. 11,13 Hormone replacement by means of daily injection of human recombinant metreleptin leads to rapid reductions in hyperphagia, fat mass, and metabolic and endocrine abnormalities. 2,3,10-12 Some patients have immunologic alterations. 9 Clinical hallmarks of congenital leptin deficiency include early-onset extreme obesity, marked hyperphagia, and hormonal as well as metabolic disturbances. The type I cytokine leptin is mainly produced by adipocytes to signal the energy state of the body and exerts its function as a satiety signal in the hypothalamus. Seven additional mutations have since been reported. 2 The conditions of both children were characterized by the absence of leptin in the circulation as a result of a homozygous frameshift mutation in LEP. 1 It was first described in two extremely obese cousins from a consanguineous Pakistani family. The most trusted, influential source of new medical knowledge and clinical best practices in the world.Ĭongenital leptin deficiency is a very rare cause of early-onset extreme obesity. ![]() Information and tools for librarians about site license offerings. Valuable tools for building a rewarding career in health care. The authorized source of trusted medical research and education for the Chinese-language medical community. The most advanced way to teach, practice, and assess clinical reasoning skills. Information, resources, and support needed to approach rotations - and life as a resident. The most effective and engaging way for clinicians to learn, improve their practice, and prepare for board exams. NEW! Peer-reviewed journal featuring in-depth articles to accelerate the transformation of health care delivery.Ĭoncise summaries and expert physician commentary that busy clinicians need to enhance patient care. NEW! A digital journal for innovative original research and fresh, bold ideas in clinical trial design and clinical decision-making. ![]()
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