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Pulmonary Veno-occlusive Disease Caused by an Inherited Mutation in Bone Morphogenetic Protein Receptor II

Division of Allergy, Pulmonary and Critical Care, Department of Medicine and Departments of Pathology and Pediatrics and Genetic Medicine, Vanderbilt University Medical Center, Nashville, Tennessee; and Division of Human Genetics, Children's Hospital Medical Center, Cincinnati, Ohio

Correspondence and requests for reprints should be addressed to James R. Runo, M.D., Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, T-1217 Medical Center North, Nashville, TN 37232-2650. E-mail: james.runo{at}mcmail.vanderbilt.edu

ABSTRACT

Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension in which the vascular changes originate in the small pulmonary veins and venules. The pathogenesis is unknown and any link with primary pulmonary hypertension (PPH) has been speculative. Mutations in the bone morphogenetic protein receptor II (BMPR2) gene have been identified in at least 50% of familial cases and in 25% of sporadic cases of PPH. We report a patient with documented PVOD whose mother had severe pulmonary hypertension. Sequencing of the patient's BMPR2 coding region revealed a del44C mutation in Exon 1 that is predicted to encode for a truncated protein. Analysis of DNA from family members suggests that this mutation was transmitted by the proband's mother to two of her four children. The finding of PVOD associated with a BMPR2 mutation reveals a possible pathogenetic connection with PPH.

Key Words: primary pulmonary hypertension • pulmonary hypertension • pulmonary veno-occlusive disease • genetic mutation • bone morphogenetic protein receptor II

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