|
|
||||||||
Depts of 1 Medicine, 2 Psychiatry, 3 Pediatrics, and the 4 Columbia Genome Center, Columbia University College of Physicians and Surgeons, and the 5 New York State Psychiatric Institute, New York, NY, USA
CORRESPONDENCE: J.H. Morse, Dept of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, USA. Fax: 1 2123054943. E-mail: jhm4@columbia.edu
Keywords: Bone morphogenetic protein receptor 2 mutations, congenital heart defects, eisenmenger syndrome, pulmonary hypertension
Received: February 13, 2004
Accepted May 12, 2004
This study was supported by the Stony Wold-Herbert Foundation (K.E. Roberts), the Pulmonary Hypertension Association (W.P.K. Wong) and National Institute of Health-Heart Lung 60056 (J.H. Morse).
The aim of the present study was to determine if patients with both pulmonary arterial hypertension (PAH), due to pulmonary vascular obstructive disease, and congenital heart defects (CHD), have mutations in the gene encoding bone morphogenetic protein receptor (BMPR)-2.
The BMPR2 gene was screened in two cohorts: 40 adults and 66 children with PAH/CHD. CHDs were patent ductus arteriosus, atrial and ventricular septal defects, partial anomalous pulmonary venous return, transposition of the great arteries, atrioventicular canal, and rare lesions with systemic-to-pulmonary shunts.
Six novel missense BMPR2 mutations were found in three out of four adults with complete type C atrioventricular canals and in three children. One child had an atrial septal defect and patent ductus arteriosus; one had an atrial septal defect, patent ductus arteriosus and partial anomalous pulmonary venous return; and one had an aortopulmonary window and a ventricular septal defect.
Bone morphogenetic protein receptor 2 mutations were found in 6% of a mixed cohort of adults and children with pulmonary arterial hypertension/congenital heart defects. The current findings compliment recent reports in mouse models implicating members of the bone morphogenetic protein/transforming growth factor-ß pathway inducing cardiac anomalies analogous to human atrioventricular canals, septal defects and conotruncal congenital heart defects. The small number of patients studied and the ascertainment bias inherent in selecting for pulmonary arterial hypertension require further investigation.
This article has been cited by other articles:
![]() |
A. E. Ashley-Koch, L. Elliott, M. E. Kail, L. M. De Castro, J. Jonassaint, T. L. Jackson, J. Price, K. I. Ataga, M. C. Levesque, J. B. Weinberg, et al. Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease Blood, June 15, 2008; 111(12): 5721 - 5726. [Abstract] [Full Text] [PDF] |
||||
![]() |
M. T. Nasim, A. Ghouri, B. Patel, V. James, N. Rudarakanchana, N. W. Morrell, and R. C. Trembath Stoichiometric imbalance in the receptor complex contributes to dysfunctional BMPR-II mediated signalling in pulmonary arterial hypertension Hum. Mol. Genet., June 1, 2008; 17(11): 1683 - 1694. [Abstract] [Full Text] [PDF] |
||||
![]() |
J. Suntharalingam, R. D Machado, L. D Sharples, M. R Toshner, K. K Sheares, R. J Hughes, D. P Jenkins, R. C Trembath, N. W Morrell, and J. Pepke-Zaba Demographic features, BMPR2 status and outcomes in distal chronic thromboembolic pulmonary hypertension Thorax, July 1, 2007; 62(7): 617 - 622. [Abstract] [Full Text] [PDF] |
||||
![]() |
G.-P. Diller and M. A. Gatzoulis Pulmonary Vascular Disease in Adults With Congenital Heart Disease Circulation, February 27, 2007; 115(8): 1039 - 1050. [Abstract] [Full Text] [PDF] |
||||
![]() |
N. W. Morrell Pulmonary Hypertension Due to BMPR2 Mutation: A New Paradigm for Tissue Remodeling? Proceedings of the ATS, November 1, 2006; 3(8): 680 - 686. [Abstract] [Full Text] [PDF] |
||||
![]() |
K. Ihida-Stansbury, D. M. McKean, K. B. Lane, J. E. Loyd, L. A. Wheeler, N. W. Morrell, and P. L. Jones Tenascin-C is induced by mutated BMP type II receptors in familial forms of pulmonary arterial hypertension Am J Physiol Lung Cell Mol Physiol, October 1, 2006; 291(4): L694 - L702. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Provencher, X. Jais, A. Yaici, O. Sitbon, M. Humbert, and G. Simonneau Clinical Challenges in Pulmonary Hypertension: Roger S. Mitchell Lecture Chest, December 1, 2005; 128(6_suppl): 622S - 628S. [Abstract] [Full Text] [PDF] |
||||
![]() |
S. Provencher, X. Jais, A. Yaici, O. Sitbon, M. Humbert, and G. Simonneau Clinical Challenges in Pulmonary Hypertension: Roger S. Mitchell Lecture Chest, December 1, 2005; 128(6_suppl): 622S - 628S. [Abstract] [Full Text] [PDF] |
||||
![]() |
R. E. Harrison, R. Berger, S. G. Haworth, R. Tulloh, C. J. Mache, N. W. Morrell, M. A. Aldred, and R. C. Trembath Transforming Growth Factor-{beta} Receptor Mutations and Pulmonary Arterial Hypertension in Childhood Circulation, February 1, 2005; 111(4): 435 - 441. [Abstract] [Full Text] [PDF] |
||||
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |