Severe Early Onset Obesity due to a Novel Missense Mutation in Exon 3 of the Leptin Gene in an Infant from Northwest India

Monogenic obesity, caused by mutations in one of the genes involved in the control of hunger and satiety, is a rare cause of early onset obesity (EOO). The most common of the single gene alterations affect the leptin gene ( LEP ), resulting in congenital leptin deficiency that manifests as intense hyperphagia, EOO and severe obesity associated with hormonal and metabolic alterations. Only eight mutations of ( LEP associated with congenital leptin deficiency have been described in humans to date. In this study, we report a novel, homozygous, missense mutation in exon 3 of the ( LEP gene (chr7:127894610;c.298G>A) resulting in the amino acid substitution of asparagine for aspartic acid at codon 100 (p.Asp100Asn) in a 10-month-old infant who presented to us with severe hyperphagia and EOO. She was subsequently found to have low serum leptin concentrations. Additionally, a homozygous missense variation of unknown significance in exon 11 of Bardet-Biedl syndrome-1 gene (chr11:66291279; G>A; Depth 168x) was detected. Significant abnormalities of lipid parameters were also present in our patient. Both parents were thin but there was a family history suggestive of EOO in a paternal uncle and a cousin. In conclusion, we report the second patient from India with a novel mutation of the ( LEP gene associated with severe obesity.