Pulmonary veno-occlusive disease caused by an inherited mutation in bone morphogenetic protein receptor II.
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.
Runo
James R
JR
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
Vnencak-Jones
Cindy L
CL
Prince
Melissa
M
Loyd
James E
JE
Wheeler
Lisa
L
Robbins
Ivan M
IM
Lane
Kirk B
KB
Newman
John H
JH
Johnson
Joyce
J
Nichols
William C
WC
Phillips
John A
JA
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
D000959:Antihypertensive Agents; D005819:Genetic Markers; D011464:Epoprostenol; D017346:Protein Serine-Threonine Kinases; C498218:BMPR2 protein, human; D052006:Bone Morphogenetic Protein Receptors, Type II