Abstract
Mutations of the bone morphogenetic protein receptor 2 (BMPR2) predispose to pulmonary arterial hypertension (PAH). 290 idiopathic PAH (IPAH) and 15 heritable PAH (HPAH) were screened to determine BMPR2 mutations spectrum and rate in a large Chinese patient group.
Gene sequencing and multiplex ligation-dependent probe amplification (MLPA®) were used to detect sequence mutations and large rearrangements (RGTs). Total mutation rate was 14.5% (n=42 of 290) in Chinese IPAH patients, and 53.3% (n=8 of 15) in HPAH patients. RGT mutation rate was 3.1% (n=7 of 229) and represented 14% (n=7 of 50) of all identified mutations. Twenty-five BMPR2 mutations were newly identified.
Patients were younger than other reported PAH subjects, and BMPR2 mutation carriers were around 6 years younger at diagnosis than non-carriers (P=0.002), but this relationship was significant only in the female group which was larger. The proportion of females carrying a BMPR2 mutation was two-fold lower than in males (12.8% versus 25.3%; P=0.008).
Our results indicate the overall genetics of Chinese PAH patients is similar to that of other populations, but the clinical picture differs by the precocity of the disease in the whole patient group, and the lower proportion of females found to carry a BMPR2 mutation.
- ERS
