Leptin receptor deficiency - LEPR gene

The leptin receptor deficiency is associated with severe process from the first months of life obesity. Affected individuals have normal weight at birth, but are constantly hungry and gain weight quickly. Without treatment, hunger continues with a permanent overeating that causes obesity. From early childhood, affected individuals develop abnormal eating behaviors such as fighting with other children for food, hoarding food and eat in secret. People with leptin receptor deficiency also have hypogonadotropic hypogonadism, due to reduced production of hormones that direct sexual development. Untreated, affected individuals have delayed puberty or through puberty and can be infertile.


The leptin receptor deficiency is due to mutations in the gene LEPR (Leptin receptor), located on the short arm of chromosome 1 (1p31). This gene encodes a so - called leptin receptor, which is also involved in regulating body weight protein. Protein leptin receptor is on the surface of cells in many organs and tissues, including the hypothalamus.


The leptin receptor is activated by leptin, when bound to the receptor. Normally, fat cells (adipocytes) in the body release leptin in proportion to its size. As the fat accumulates in the cells, more leptin is produced. This increase indicates that leptin fat reserves are increasing. Leptin aggregates bind and activate the leptin receptor. The hypothalamus controls hunger and thirst, as well as other functions such as sleep, mood, and body temperature. It also regulates the release of hormones that have many functions throughout the body. In the hypothalamus, the binding of leptin to its receptor triggers a series of chemical signals that affect feelings of hunger and help produce a feeling of satiety.


They have been described at least 18 mutations in the gene associated with LEPR leptin receptor deficient (11 missense mutations, 1 mutation cutting / splicing -splicing-; 1 small insertion; 1 greater insertion / duplication; 1 repeat variation) . Mutations in the gene LEPR prevent the receptor respond to leptin, which leads to weight gain and excessive hunger associated with this condition. Due to hypogonadotropic hypogonadism that occurs in the deficiency of leptin receptor, it is believed that signaling leptin receptor is also involved in regulating the body's response to hormones that control sexual development, and that this response is affected by mutations in the gene LEPR. However, the mechanism of this effect is unknown.


This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.

Tests in IVAMI: in IVAMI perform detection of mutations associated with leptin receptor deficiency, by complete PCR amplification of the exons of the gene LEPR, and subsequent sequencing.


Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).