A 25-year-old woman has had progressive dyspnea and fatigue for the past 2 years. On physical examination, she has pedal edema, jugular venous distention, and hepatomegaly. Lung fields are clear on auscultation. Chest CT scan shows right heart enlargement. Cardiac catheterization is performed, and the pulmonary arterial pressure is increased, without gradients across the pulmonic valve, and no shunts are noted. A transbronchial biopsy is performed, and microscopic examination shows plexiform lesions. A mutation in a gene encoding for which of the following is most likely to cause her pulmonary disease?
Correct Answer: Bone morphogenetic receptor 2 (BMPR2)
Description: The finding of pulmonary hypertension in a young individual without any known pulmonary or cardiac disease is typical for primary pulmonary hypertension. The increased pulmonary arterial pressure leads to hypertrophy of the right side of the heart. The large pulmonary arteries show atherosclerosis; the arterioles show plexogenic arteriopathy with a tuft of capillary formations producing a network, or web, that spans the lumens of dilated thin-walled arteries. BMPR2, a cell surface protein belonging to the TGF-b receptor superfamily, causes inhibition of vascular smooth muscle cell proliferation and favors apoptosis. In the absence of BMPR2 signaling, smooth muscle proliferation occurs, and pulmonary hypertension ensues. Inactivating germline mutations in the BMPR2 gene are found in 50% of the familial (primary) cases of pulmonary hypertension and in 26% of sporadic cases. None of the other molecules listed regulate pulmonary arterial wall structure. Endothelial nitric oxide controls vascular caliber. B-type natriuretic peptide and renin regulate sodium and water homeostasis, plasma volume, and systemic arterial pressure. Mutation in the gene for fibrillin-1 (FBN1) occurs in Marfan syndrome. Lysyl hydroxylase is required for cross-linking collagen, and its loss gives rise to one form of Ehlers-Danlos syndrome.
Category:
Pathology
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