Investigating molecular mechanisms of a new ultra-rare syndrome with intellectual disability
Populärvetenskaplig sammanfattning av projektet
The individuals we are interested in are typically one in a million, and they are exceptional in their genetic make-up. When we study their genomes, we learn and understand how a cell works properly and how a little change in the genetic code disturbs the harmony in the cell. So, studying the genetic make-up of these exceptional individuals helps us understand the mechanisms behind their disease and brings up new questions such as can we find a treatment? Through identifying genes behind diseases, we can discover new drug targets and find new ways to treat diseases.
We identified one of these exceptional individuals. He is a young boy with an unknown syndrome and has intellectual disability, immunodeficiency, dysmorphic features and short stature among many others. I analyzed his entire genome and found an ultra-rare variant specific to Swedish population in both copies of a well-known tumor-suppressor gene, FLCN. The mutations in this gene are known to cause Birt-Hogg-Dubé (BHD) syndrome. However, our patient does not have any features of BHD syndrome. So, I believe that the patient’s variant is a specific type and the disease mechanism is different than what we know in the case of BHD syndrome. Therefore, I want to confirm our finding by performing experiments at RNA, protein and cellular level to understand how the identified variant changes the protein structure, function and localization in the cell. I hypothesize that this variant should cause the novel unknown syndrome with immunodeficiency and intellectual disability with a different molecular mechanism. After many years of genetic odyssey, I hope the patient and his family will receive a diagnosis. Studying this ultra-rare variant will help us further understand the role of FLCN in the development and maintenance of different cell types. Furthermore, this new knowledge may contribute to discoveries of new drugs and treatments.