News items Genfunctie muteert vaker dan gedacht
1 September 2017

Intellectual disabilities are often caused by a mutation that damages a gene, preventing the associated protein from functioning properly. However, a mutation can also change the function of a gene. As a result, the gene in question acts in a completely different way. Researchers from Radboudumc discovered this mechanism in fifteen genes playing a role in the development of intellectual disabilities. Their research results published in the American Journal of Human Genetics on 31 August 2017 show that these changes in function play a more prominent role than previously thought.

Genes are responsible for protein production in cells. A common cause of intellectual disabilities is a de novo mutation (i.e. a mutation present in a child, but not in its parents) damaging a gene so severely that it is no longer able to produce functional proteins. The resulting protein defect will cause illness. In a number of disease-related genes, it is shown that a de novo mutation does not eliminate the gene, but probably alters its function. These mutations are only located on specific parts of the gene.
 
Change in function
In order to find out how often this mechanism is involved, researchers from Radboudumc have combined the gene mutations in Dutch patients with a large international database comprising de novo mutations in patients. This research project was led by geneticist Christian Gilissen. “With our method, we were able to detect genes in which mutations not so much eliminate as affect the gene in another way. We found fifteen genes in which mutations cluster closely together, twelve of which being associated with developmental disorders. We also found three new genes that are likely to play a role in the development of intellectual disabilities as well”, according to Gilissen.
 
Interactions   
The de novo mutations that were found only change a very small part of a protein. The function of the protein remains largely, but not entirely the same. Gilissen says: “The mutations are more likely to affect superficial parts of the proteins. These disturb interactions with other proteins and cause problems. Although mutations eliminating genes were often thought to be the main cause of intellectual disabilities, mutations altering the function of genes are now shown to be an important factor as well. That is a surprising finding.”
 
Clustering mutations           
Why are the de novo mutations that were found specifically clustered? Gilissen says: “There can be several explanations for that. Firstly, these genes show little natural variation. If such a gene is completely eliminated, a person may not be born. Only mutations located on very specific parts of the gene are viable. Consequently, only these mutations can be found. Another explanation can be that the mutations provide growth benefits to the sperm in which they develop. In that case, only these mutations would be able to survive.”
 
New possibilities     
The three newly-discovered genes playing a role in the development of intellectual disabilities provide new diagnostic possibilities for patients. Gillissen says: “It is important that we have discovered a mechanism that has not yet been a focus of study. We expect this mechanism to play a role in a much larger proportion of patients with intellectual disabilities.”

More information


Marcel Wortel

information officer

(024) 81 87389

Related news items


European Commission Initiative on Breast Cancer (ECIBC) Guidelines

13 August 2019

In Annals of internal medicine Mireille Broeders and colleagues from the ECIBC Guidelines Development Group described the methods used to develop person-centered evidence-based recommendations for screening and diagnosis of breast cancer.

read more

Circulation publication for exercise physiologists

13 August 2019

Thijs Eijsvogels and Vincent Aengevaeren showed that exercise-incuded elevations of troponin concentrations are predictive of major adverse cardiovascular events and mortality.

read more

DELA, Radboudumc and Games for Health start a new project to fight loneliness among elderly using games

12 August 2019

More than half of people aged 75 and over feel their selves lonely every now and then. A special collaboration between DELA, Radboudumc, and Games for Health will investigate whether joined gaming between elderly and young people can alleviate this social problem.

read more

Floris Schreuder received Dekker grant

6 August 2019

Floris Schreuder received one of the ten Dekker grants from the Dutch Heart Foundation (Hartstichting).

read more

A warm welcome for a new RIMLS colleague Nico Sommerdijk

5 August 2019

As of 1 August we welcome Nico Sommerdijk as our new colleague at the RIMLS. Nico will join the department of Biochemistry, with his research group “Biochemistry of Mineralized Tissues”.

read more

Bart Kiemeney finishes 1st in the Tour and raises thousands of euros

30 July 2019

With over €43,000 on the counter, Kiemeney can see the Tour de France as a great success.

read more