title: Pulmonary veno-occlusive disease caused by an inherited mutation in bone morphogenetic protein receptor II.
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.
authors.affiliation: Division of Allergy, Pulmonary and Critical Care Medicine, Vanderbilt University Medical Center, T-1217 Medical Center North, Nashville, TN 37232-2650, USA. james.runo@mcmail.vanderbilt.edu
authors.forename: James R
authors.initials: JR
authors.lastname: Runo
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Vnencak-Jones
authors.forename: Melissa
authors.initials: M
authors.lastname: Prince
authors.forename: James E
authors.initials: JE
authors.lastname: Loyd
authors.forename: Lisa
authors.initials: L
authors.lastname: Wheeler
authors.forename: Ivan M
authors.initials: IM
authors.lastname: Robbins
authors.forename: Kirk B
authors.initials: KB
authors.lastname: Lane
authors.forename: John H
authors.initials: JH
authors.lastname: Newman
authors.forename: Joyce
authors.initials: J
authors.lastname: Johnson
authors.forename: William C
authors.initials: WC
authors.lastname: Nichols
authors.forename: John A
authors.initials: JA
authors.lastname: Phillips
mesh_terms: D000328:Adult; D000959:Antihypertensive Agents / Q000627:therapeutic use; D001706:Biopsy; D052006:Bone Morphogenetic Protein Receptors, Type II; D006328:Cardiac Catheterization; D004252:DNA Mutational Analysis; D018900:Dinucleotide Repeats / Q000235:genetics; D004417:Dyspnea / Q000209:etiology; D011464:Epoprostenol / Q000627:therapeutic use; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D006976:Hypertension, Pulmonary / Q000209:etiology; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D011668:Pulmonary Veno-Occlusive Disease / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy / Q000235:genetics*; D017422:Sequence Analysis, DNA; D014057:Tomography, X-Ray Computed
chemical_list: D000959:Antihypertensive Agents; D005819:Genetic Markers; D011464:Epoprostenol; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II