Which mutation is associated with primary pulmonary hypertension?

• A. Trisomy 21
• B. JAK2 mutation
• C. CFTR mutation
• D. BMPR2 mutation

Answer: (D)

BMPR2 mutation is the best explanation for primary pulmonary hypertension because this condition is often linked to genetic changes that affect the pulmonary blood vessels’ growth and structure. BMPR2 encodes a receptor in the BMP signaling pathway, which normally helps regulate the balance between smooth muscle cell proliferation and programmed cell death in the pulmonary arteries. When this signaling is impaired by a BMPR2 mutation, there is excessive proliferation and reduced apoptosis of vascular cells, leading to narrowing and remodeling of small pulmonary arteries. This remodeling raises pulmonary vascular resistance and pressures, driving the development of idiopathic (primary) PAH. The mutation is classically associated with familial PAH and is a major genetic contributor to the idiopathic form, though penetrance is incomplete.

Trisomy 21 can be associated with pulmonary hypertension, but usually through other factors such as congenital heart disease or prematurity rather than primary PAH. JAK2 mutations relate to myeloproliferative disorders and can lead to secondary PH (for example, via thrombosis or vascular changes), not the primary form. CFTR mutations are linked to cystic fibrosis–related lung disease, which can involve PH secondarily.