Fibrodysplasia ossificans progressiva
Patients with the rare genetic disorder FOP have bones growing in their muscles, ligaments, tendons and other tissues. There are usually no signs of the condition at birth, apart from malformations of the big toe. Symptoms can become apparent from the age of 5 onwards. As the bones grow abnormally through joints and connective tissue they form bridges, causing stiffness and in many cases severely restricting movement. Eventually the patient becomes imprisoned by a second skeleton.
Many areas of the body are affected including the neck, spine, chest, shoulders, elbow, ankles, knees and jaw. And it doesn’t help matters if the excess bone is cut away. It just results in an explosion of bone growth in unwanted areas. Even bumps and bruises can cause tissue to turn to bone.
Basic genetics of FOP
FOP is an autosomal dominant condition and that means than an individual only needs to inherit one gene for FOP to have this genetic disorder. There has been much work during recent years to try and understand more about its basic genetics.
In 2006 a team of researchers from the University of Pennsylvania School of Medicine found the gene, that when mutated, causes the symptoms of FOP. The gene is for a receptor called ACVR1 in the bone morphogenetic protein-signalling pathway (BMP). It’s situated on chromosome 2 and is highly conserved in vertebrates. BMP proteins are involved in the embryonic development of the skeleton as well as post-natal repair.
The mutation that leads to this rare genetic disorder is a single nucleotide substitution in the ACVR1 gene; and this leads to the ACVR1 protein being incorrectly made. What happens is that the amino acid histidine is substituted for the amino acid arginine at one specific position, and this leads directly to the development of FOP.
At the present time there is no cure or treatment for FOP. But there is some good news. The discovery of the gene that causes the dramatic symptoms of this rare genetic disorder provides a very specific target for a potential drug therapeutic. Such a therapy could reverse or put a stop to the development of symptoms.