Homozygosity for two missense mutations in the leptin receptor gene (P316:W646C) in a Turkmenian girl with severe early-onset obesity.

Leptin receptor gene mutations are a very rare cause of severe early-onset obesity. They are also associated with lack of pubertal development and intense hyperphagia. Presented here is a case of a 6-year-old Turkmenian girl with monogenic obesity due to a congenital deficiency of the leptin receptor. She was born from a consanguineous marriage of second cousins after 40 gestational weeks following an uncomplicated pregnancy. Her birth weight was 3500 g. However, rapid weight gain was observed after 6 months. On presentation she was 130 cm tall [> 97th percentile; standard deviation score (SDS): +2], with a weight of 90 kg (> 97th percentile; SDS: +5.3) and a body mass index (BMI) of 53.2 kg/m2 (SDS: +3.6). Results of genetic evaluation revealed the patient to be homozygous for two missense mutations in the leptin receptor gene (P316T;W646C) resulting in complete loss of leptin receptor function. Both parents were heterozygous for the same pair of missence mutations.