Elevated levels of PGE2 in PDP patients are associated with mutations of HPGD gene. These patients showed typical PDP symptoms such as digital clubbing and periostosis. The HPGD gene is mapped on chromosome 4q34 and encodes the enzyme HPGD (15-hydroxyprostaglandin dehydrogenase). This enzyme catalyzes the first step in the degradation of PGE2 and related eicosanoids. So far, eight different mutations are known leading to a dysfunctional HPGD enzyme in PDP patients. Due to these mutations, the binding of the substrate PGE2 to HPGD is disrupted. As a result of this, PGE2 cannot be transferred into PGE-M down and remain present at high concentrations.