Fibrodysplasia Ossificans Progressiva - Causes

Causes

FOP is caused by an autosomal dominant allele on chromosome 2q23-24. The allele has variable expressivity, but complete penetrance. Most cases are caused by spontaneous mutation in the gametes; most people with FOP cannot have children. A study has determined that it affects approximately 1 in every 2 million people. A similar but less catastrophic disease is fibrous dysplasia, which is caused by a post-zygotic mutation.

A mutation in the gene ACVR1 (also known as activin-like kinase 2 ) is responsible for the disease. ACVR1 encodes activin receptor type-1, a BMP type-1 receptor. The mutation changes codon 206 from arginine to histidine in the ACVR1 protein. This causes endothelial cells to transform to mesenchymal stem cells and then to bone.