Leptin, a 167-amino acid protein produced by the LEP gene is located on chromosome 7q31.3. They also develop metabolic and hormonal alterations including hyperinsulinemia, insulin resistance, severe liver steatosis, dyslipidemia, and hypogonadotropic hypogonadism. Children with CLD have normal birth weight but rapidly gain weight in the first months of life leading to extreme obesity, impaired satiety and intense hyperphagia. However, a homozygous mouse leptin V145E mutant genotype ( LEP V145EV/145E) with high circulating leptin levels has been described. Mutations in the mouse leptin gene lead to severe obesity and, in nearly all cases, very low plasma leptin concentration. In addition to regulating food intake, leptin increases energy expenditure through sympathetic nerve activity. Leptin interacts with a complex neural circuit to control food intake, activating anorexigenic neurons that synthesize pro-opiomelanocortin (POMC) and inhibiting orexigenic neurons that synthesize agouti-related peptide (AgRP) and neuropeptide Y (NPY). Circulating leptin levels are directly in proportion to the amount of body fat, thereby reflecting the status of long-term energy stores. Leptin is secreted by adipose tissue and regulates energy homeostasis, neuroendocrine function, metabolism, immune function and other systems through its effects on the central nervous system and peripheral tissues. Conclusions: The mutation of LEP, absence of detectable leptin, and the severe obesity found in these sisters provide the first evidence of monogenic leptin deficiency reported in the continents of North and South America. Their serum leptin levels were undetectable despite their markedly elevated fat mass. Detailed information and clinical measurements of these sisters were also collected. Results: Direct sequencing of the coding region of LEP gene in the sisters revealed a novel homozygous missense mutation in exon 3, C350G>T. DNA sequencing was performed on MiSeq equipment (Illumina) of a next-generation sequencing (NGS) panel involving genes related to severe obesity, including LEP. Their serum leptin was measured by MicroELISA.

Methods: We present two severely obese sisters from Colombia, members of the same lineal consanguinity. These mutations may cause nonsense-mediated mRNA decay, defective secretion or the phenomenon of biologically inactive leptin, but typically lead to an absence of circulating leptin, resulting in a rare type of monogenic extreme obesity with intense hyperphagia, and serious metabolic abnormalities. It is caused by mutations in the leptin ( LEP) gene, which encodes the protein product leptin. Background: Congenital leptin deficiency is a recessive genetic disorder associated with severe early-onset obesity.

Lepton gene