Gene mutations seem to occur in the majority of families with familial pulmonary arterial hypertension (PAH), according to a study reported in an Italian abstract.
PAH is a rare disease characterised by elevation of pulmonary vascular resistance and resulting in right ventricular failure and premature death. While more than 90% of patients with idiopathic PAH have no known family history, the NIH registry on idiopathic PAH, published in the early 1990s, found that 6% did.
Germline mutations in bone morphogenetic protein receptor type 2 gene (BMPR2), known to encode for the receptor of a specific metabolic pathway involved in the control of cellular proliferation and apoptosis, have been found in familial PAH (FPAH) patients. The mutation predisposes individuals to uncontrolled cell proliferation, and BPPR2 receptors have been found to be widely expressed in the pulmonary circulation.
The study reported by Professor Nazzareno Galie and colleagues from University of Bologna set out to investigate the frequency of BMPR2 gene mutations in families with more than one case of idiopathic PAH, known as clinical FPAH, and in consecutive cases without a family history, known as clinical sporadic idiopathic PAH.
In the study 40 probands of 11 families - consisting of 16 affected individuals and 24 unaffected relatives - and 72 consecutive sporadic IPAH patients were assessed for BMPR2 mutations using DNA extracted from venous blood. Firstly, denaturing high-pressure liquid chromatography was used to identify the majority of mutations, then Multiplex Ligation-dependent Probe Amplification was used to identify large gene rearrangements which might have been missed by the first assessment. All participants were subjected to right heart catheterisation to assess pressure inside the pulmonary artery, and establish diagnosis.
Results showed that mutations were identified in eight of the 11 families (73%) and seven of 72 sporadic idiopathic PAH patients (11%). The mutation was also found in six of 24 unaffected relatives. Furthermore, results revealed a younger age for PAH patients with the BMPR2 mutation than without (50 ±19 versus 36 ±17, P=0.001); and higher mean pulmonary arterial pressure for patients with the mutation than those without ( 65 ±22 mmHg versus 57 ±14 mmHg, P=0.07).