Patients with BPTA syndrome have characteristically malformed limbs featuring short fingers and additional toes, missing tibia bones in their legs and reduced brain size.
Most proteins are found in separate protein-rich droplets called “cellular condensates” in cells. These proteins carry sequence characteristics that serve as address labels, informing the protein which condensates to move into. Proteins may wind up in the wrong condensate if the labels are messed up. According to a multinational team of clinical medicine and fundamental biology researchers, this could be the source of many unresolved disorders.
Patients with BPTA syndrome have characteristically malformed limbs featuring short fingers and additional toes, missing tibia bones in their legs and reduced brain size. As the researchers found out, BPTAS is caused by a special genetic change that causes an essential protein to migrate to the nucleolus, a large proteinaceous droplet in the cell nucleus. As a result, the function of the nucleolar condensate is inhibited and developmental disease develops.
“What we discovered in this one disease might apply to many more disorders. It is likely not a rare unicorn that exists only once. We just could not see the phenomenon until now because we did not know how to look for it,” says Denise Horn, a clinical geneticist at the Institute of Medical and Human Genetics at Charite – Universitatsmedizin Berlin.
In collaboration with scientists at the Max Planck Institute for Molecular Genetics (MPIMG) in Berlin, the University Hospital Schleswig-Holstein (UKSH), and contributors from all around the world, the team is pushing open a door to new diagnoses that could lead to the elucidation of numerous other diseases as well as possible future therapies.
“We discovered a new mechanism that could be at play in a wide range of diseases, including hereditary diseases and cancer,” says Denes Hnisz, Research Group Leader at the MPIMG. “In fact, we have discovered over 600 similar mutations, 101 of which are known to be associated with different disorders.”
“The actual work is just starting now,” adds human geneticist Malte Spielmann of UKSH in Lubeck and Kiel. “We will find many more genes with such disease-causing mutations and can now test their mode of action.”
