"Genomics & Algorithms for Rare Diseases" Interview with Prof. Guillaume Smits and Romain Alderweireldt

GEMVAP, 2021 / Tuesday, December 29th, 2020

This interview was published in " Le Chaînon - the magazine of patients' and relatives' associations "LUSS, No. 52 in September 2020.

Le Chaînon (LC): Romain, together with Ludivine Verboogen, you created Fondation 101 Génomes (F101G) which aims to promote genomic research in the field of rare diseases. Why did you create this foundation?

Romain Alderweireldt (RA): We started this foundation because my son suffers from a neonatal form of Marfan syndrome. The statistical life expectancy of the few known cases of this form of the disease is barely 16 months.

It was in this difficult context that I became interested in genomic research and that the F101G was created.

LC: What did you learn?

RA: In reviewing a genetic database of 'healthy' individuals that serve as research controls, I found that it contained many variants on the FBN1 gene that are considered to be 'pathogenic' variants that cause Marfan syndrome.

LC: Professor Guillaume Smits, what does this observation imply?

Guillaume Smits (GS): The discovery of apparently healthy individuals (or individuals with such low penetrance of the disease that they are unaware of being ill) with pathogenic variants raises the possibility that they are genetically protected from even the most severe forms of Marfan syndrome by the action of a so-called protective gene that can counteract the failure of the FBN1 gene that causes the disease.

LC: Could the identification of this mechanism lead to the development of new treatments?

GS: Potentially, yes. But we still have to identify it within the genome, which is no easy task! And before that, we have to check whether the mutations identified are not the result of classification errors.

LC: How do we do this?

GS: With (ib)², we developed an algorithm to check all conceivable mutations in the FBN1 gene using artificial intelligence. This bioinformatics tool confirmed that several mutations identified by Romain are pathogenic.

LC: What to do next?

GS: The tool we have in place could already be improved to help with the diagnosis of Marfan syndrome. If we could have access to genomic data of people with pathogenic mutations in whom the penetrance of the disease is low, we could use the bioinformatics tools developed with Professor Tom Lenaerts to identify a possible protective gene.

This gene would make it possible to envisage new therapeutic avenues that would replicate its protective effects.

RA: The possibility that some people's genomes hold the keys to curing children with rare diseases led to the creation of Fondation 101 Génomes , whose mission is to make it easier for scientists to access the genomes of patients with rare diseases.

By Romain ALDERWEIRELDT, father of a little boy suffering from Marfan syndrome, representative of the Belgian Marfan Syndrome Association to VASCERN and founder of Fondation 101 Génomes and by Professor Guillaume SMITS, geneticist, Director of the Centre for Human Genetics of the ULB and founding member of the Interuniversity Institute of Bioinformatics of Brussels (ib)².

For more information: Fondation 101 Génomes : www.f101g.org | (ib)² : https://ibsquare.be/


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