They find new mutations in a gene that causes severe obesity in children

In many industrialized nations, a worrying percentage of minors are obese.

In Argentina, for example, 20.4 percent of children and adolescents suffer from obesity. These data arise from the Second National Nutrition and Health Survey (ENNYS 2), carried out in 2019, and reflect a problem with several edges. Among them, a type of obesity different from the common one stands out, called monogenic obesity, which is caused by mutations in the genes responsible for regulating food intake and whose population is underdiagnosed.

Seeking to provide an answer to this problem, a group of scientists from the Multidisciplinary Institute of Cell Biology (IMBICE) is dedicated to studying these mutations of the gene that encodes the melanocortin 4 receptor (MC4R), in a population of children with obesity. To do this, they worked with samples taken from 78 patients at the Children’s Hospital in La Plata and, as a result of the first instance of the study, they found three new mutations that, until now, had not been reported anywhere in the world.

“Mutations occur randomly due to failures during cell division and are passed from parent to child. In the case of the boys where we found this, we were able to also analyze their parents and we found, in two cases, that the mothers were the carriers of this mutation and another in a father. In general, it coincides with a previous history of obesity”, explains Florencia Di Rocco, a researcher at the Scientific Research Commission (CIC) and a member of the team, in dialogue with Agencia CTyS – UNLaM.

The IMBICE group of scientists is made up of Florencia Di Rocco, Jesica Raingo, Estefanía Fernández, Clara McCarthy and Silvia Susana Rodríguez. (Photo: CIC)

a troublesome gene

Unlike traditionally diagnosed multifactorial obesity, in which the factors that intervene can be genetic, but also environmental or related to a sedentary lifestyle and the intake of inappropriate foods, in monogenic obesity the main component is genetic.

“It is a type of obesity, in general, more severe. It starts much earlier, boys sometimes from the first months and years of life begin to gain weight and this occurs because they are voraciously hungry, which is called ‘hyperphagia’. This gene (MC4R) is very important in controlling appetite. What mutations produce is that there is no signal of satiety, ”he highlights.

What aggravates the situation of people who suffer from this type of disease is the difficulty in accessing a correct diagnosis, since the only way to detect it is through a genetic test. “The study is simple because it is a very small gene, the problem is that it is not usually done in hospitals, it is not a routine test that pediatricians or nutritionists order because it is not a frequent disease and, mainly, due to the absence of information. For this reason, it seems important to us that, in the future, we can offer this service from IMBICE”, says Di Rocco.

This situation, according to the CIC researcher, means that this population is under-diagnosed and undergoes conventional treatments, such as a diet and physical exercise activities, which yield few results. “There is a medication that is already approved in other countries to treat cases of monogenic obesity. It has not yet arrived in our country, but it will surely be available in the not too distant future”, she predicts.

The child population, in the crosshairs

Currently, few figures are known about the number of children and adolescents suffering from monogenic obesity. The scientists estimate that, in the child population, there are more than twenty thousand affected by this pathology in the province of Buenos Aires. “This estimate arises from knowing that, in the rest of the world, between 0.5 and 5 percent of cases of obesity in boys may be of this type. So, based on the general frequency of obesity that we have here, we calculate that it may be close to that number”, he points out.

In order to search for other possible mutations in MC4R and a better estimate of the prevalence of the disease, the study will soon be extended to 120 patients at the Sor Maria Ludovica Children’s Hospital in La Plata and the Elina Specialized Subzonal Hospital in La Plata. Serna.

“Every time we find a new mutation, we have to study how they impact the functioning of the receptor to prove that it is related to the disease, because it could happen that they are harmless, that is, they do not have an impact. However, the expectation is to also find mutations that have already been described in other countries because we have a demographic history that refers to Europe and other continents and that has an impact”, he concludes. (Source: Marianela Ríos, CTyS Agency – UNLaM)