A gene called ZNRF3, known to be involved in cancer, also messes with the mind. The human brain relies on two copies of this gene to build a right-sized brain. If one of the copies is defective, the brain will be either too small or too large - known as mirror effect -, leading to various neurological symptoms.
Almost a decade ago, we saw a patient suffering from a very rare condition with an abnormally small brain, speech delay and ectodermal dysplasia - an inborn condition that affects hair, nails, teeth and skin. We sequenced part of her DNA and found a defect in one copy of the gene ZNRF3, a gene that was not yet associated with inborn disorders. This defect leads to the production of a harmful protein.
So, we suspected that this was the cause. Since then, we have collected DNA from eleven other patients from around the world who are believed to have a harmful mutation in the same gene. Most of them had a defective copy of ZNRF3 and showed variable neurodevelopmental signs with an abnormally large brain.
We tested the faulty versions of the gene in the lab and found a correlation between patients' brain size and the location of the mutations in the gene. After a long diagnostic odyssey, we were finally able to establish a definitive cause for the disease of these patients. Global collaboration enables research on rare conditions As the condition described here is extremely rare, we relied on global collaboration through professional networking databases where we posted ou.