A novel homozygous missense mutation of the leptin gene (N103K) in an obese Egyptian patient.

Congenital leptin deficiency is a rare recessive genetic disorder resulting in severe hyperphagia and early onset obesity. It is caused by mutations in the LEP gene encoding leptin. To date, only two mutations have been identified in the LEP gene, Delta133G and R105W. We present the third reported mutation identified in an Egyptian patient with very low serum leptin levels and severe early onset obesity (BMI = 51). Direct sequencing of the coding region of the LEP gene revealed a novel homozygous missense mutation, N103K. The N103K mutation was not found in 100 alleles from 50 unrelated Egyptian normal-weight control subjects using polymerase chain reaction and restriction fragment length polymorphism analysis. In conclusion, this study presents the third reported mutation of the LEP gene and will provide further insight into the physiologic role of leptin in human obesity.