Clement et al. (1998) reported a mutation in the human leptin receptor gene, a G-to-A transition at the +1 position of intron 16, that causes obesity and pituitary dysfunction. The splice site mutation results in skipping of exon 16, which leads to a truncated protein of 831 amino acids lacking both the transmembrane and intracellular domains. The mutation was discovered in homozygosity in a consanguineous Kabylian Berber family from northern Algeria in which 3 of 9 sibs had morbid obesity with onset in early childhood. The affected sisters had normal birth weights, but developed severe obesity in the first months of life. They showed abnormal eating behaviors resembling those seen in Prader-Willi syndrome and in individuals with anatomic damage of the hypothalamic area; behavior included fighting with other children for food, impulsivity, and stubbornness. Psychologic testing showed emotional lability and social disability, but no mental retardation. Core temperature and glucose metabolism were normal, as were ACTH and cortisol, but growth hormone and thyrotropin levels were low. The girls did not spontaneously develop puberty and had low estradiol, LH, and FSH levels consistent with central hypogonadism. Clement et al. (1998) considered their results to indicate that leptin is an important physiologic regulator of several endocrine functions in humans.

Uddin et al. (2009) investigated the proliferative and antiapoptotic effects of leptin receptor (Ob-R) in colorectal carcinomas (CRC). The study sought to determine Ob-R expression and its correlation with expression patterns of PI3K/AKT pathway proteins as well as other clinicopathological variables in large cohort of Saudi CRC patient samples. The researchers used tissue microarray technology to investigate 448 CRC samples taken from patients diagnosed between 1990 and 2006 in KSA. Additionally, 24 adenomas and 229 adjacent normal colorectal mucosa samples were studied using the same methodology. CRC samples displayed high prevalence of Ob-R deregulation, and Ob-R overexpression was a prognostic marker for better survival for CRC among people from the Middle East. Molecular analysis of the effects of elevated levels of Ob-R in vitro revealed that the latter can enhance the growth of colonic cancer cells and this effect is at least partially mediated by PI3K/AKT pathway.

Snoussi et al. (2006) investigated the effect of genetic variations in the LEPR gene on genetic susceptibility to and prognosis in breast cancer. A total of 308 unrelated Tunisian patients (mean age - 50 years) with primary breast cancer (unilateral tumors) with no family history of the disease, were compared to a set of 222 normal, unrelated healthy Tunisian women as control (mean age - 48 years). Genomic DNA was extracted and analyzed by PCR using primers specific to the LEPR gene, followed by RFLP using MspI. The allele frequencies of the gene in the population were found to be in Hardy Weinberg equilibrium in both groups. Carriers of 223R allele were found to have a significantly higher susceptibility to development of breast cancer. Patients showed a higher frequency of heterozygous 223QR and homozygous 223RR genotypes (0.471 and 0.211) as compared to the control group (0.405 and 0.135). The 223R allele also showed lower 3- and 6-year overall survival rate (86.76% and 75% resp.) as compared to the 223Q allele (98.5% and 97.06%). The study did not reveal any predictive value of the genotypes for clinical responses to chemotherapy. However, the authors were able to show a poorer prognosis in breast cancer for the 223R allele.