Background: Bone Morphogenic Protein Receptor 2 (BMPR2) mutations are described in patients with pulmonary arterial hypertension (PAH).
Aim: We aim to describe characteristics of BMPR2 mutations in Indian population.
Materials and methods: All patients with diagnosis of idiopathic (IPAH), hereditary (HPAH), associated with congenital heart disease(CHD) and residual PAH after CHD correction were included. BMPR2 mutation was analysed in peripheral vein blood sample by Sanger sequencing method. Study period was from January 2018 to October 2019.
Results: We analysed 46 patients (females 69.5% (32/46)), median age 26 years (0.7- 45), including 16 (34.7%) children (<18 years). The diagnosis were IPAH (33/46,71.7%), HPAH (7/46,15.2%,), PAH with associated CHD (5/46,10.8%) and residual PAH (1/46, 2.2%). 13 patients (13/46, 28.2%) had BMPR2 mutation (69.2% females) with 43.7% (7/16) of children affected. Among four families with HPAH, two had mutations, both novel. Mutation was found in 21.2% (7/33) of IPAH with one new mutation, one patient (20%) with associated CHD and the only patient with residual PAH. Patients with mutations had varied age of presentation from 0.7 years to 38 years. All patients had severe PAH at presentation with only two patients (15.3%) responding well to combination therapy, one among them had uneventful pregnancy. A HPAH patient with novel mutation refractory to combination therapy had excellent response to imatinib therapy. Other family with HPAH had novel mutation with autosomal dominant inheritance and variable penetrance resulting in asymptomatic carrier state (two patients) to severe PAH. There were two mortality.
Conclusions: In the Indian population, a patient with BMPR2 mutations may have predominantly early age of presentation with overall poor response to targeted therapy. Novel mutations were identified. HPAH associated mutation was autosomal dominant with variable penetrance. Unique response to imatinib therapy in HPAH needs to be explored.