Their excessive growth fascinates researchers. People with gigantism or acromegaly carry a common genetic mutation, which stimulates growth.
Their size blithely exceeds two meters. Giants arouse admiration and curiosity. The National Institute of Child Health and Human Development (NICHD) has discovered the genetic origin of gigantism, a rare syndrome that manifests as excessive growth that stops in adulthood. The researchers of the structure, and Prof. Albert Beckers from the University of Liège (Belgium), publish in the New England Journal of Medicine the results of over 20 years of research.
A fragment of the duplicated X chromosome
“Finding the gene responsible for the child’s excessive growth would be very helpful, but the larger question is what regulates the growth,” says lead author of the study, Constantine Stratakis. To answer this, the team analyzed the entire genome of 43 patients with gigantism. Among them, a mother and her two sons, all suffering from the disease which causes excessive growth, delayed puberty or double vision. “It is very rare to see giants. If you have three cases in the same family, it’s even rarer, ”says Dr Stratakis. Hence the importance of bringing together several patients and comparing their genetic characteristics.
Gigantism is the result of a dysfunction of the pituitary gland, a gland at the base of the brain that regulates hormones and controls the activity of other glands in the body. In some people, a tumor in the pituitary gland releases too much hormone, in others it is an overdeveloped pituitary gland. But all people with gigantism have the same defect: the duplication of a longer or shorter part of the X chromosome. In family members who do not have the syndrome, this characteristic is not present.
An overactive gene
On the abnormally duplicated parts of the X chromosome, not all genes cause gigantism. By comparing the different genomes, Dr. Albert Beckers discovered that the same four genes are duplicated in all patients. The “number one suspect” is the GPR101 gene, which is 1000 times more active in the pituitaries of sick children.
The team also screened the pituitary tumors of 248 people withacromegaly. This disease, similar to gigantism, usually manifests around the age of 30 or 40. None showed the duplication observed in giant patients… but 11 of them had a mutation in GPR101.
The next step will be to understand how the proteins expressed by this gene work. The objective: to develop new treatments for gigantism… but also for under-growth in certain children.
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