Most forms of obesity are polygenic, meaning that variations in a number of genes combined lead to an increased susceptibility to the development of obesity. However, a significant subset of cases are caused by single gene mutations (Mendelian pattern of transmission), with a growing list of mutations, including of the leptin gene (LEP), leptin receptor (LEPR) gene or melanocortin-4-receptor (MC4R) gene¹. Most of these findings were achieved utilizing the strategy of sequencing candidate genes. Nowadays, with advances in gene sequencing, including whole exome and whole genome sequencing, a more cost-effective search for mutations can be carried out, precluding the need for pre-determined candidate genes. This is certainly a very promising field.

The purpose of the present study is to identify new causal mutations for obesity. To maximize our chances of achieving this goal, the primary strategy is to search for recessive mutations in the setting of inbreeding². When these mutations are correlated with a cellular phenotype, they usually give rise to invaluable information on the underlying mechanism of a disease, potentially opening new avenues for drug development. By specifying that the recruited obese subjects come from consanguineous families where siblings and parents are not obese, we are establishing criteria that will increase our likelihood of identifying recessive mutations that cause obesity.