Clinical and Molecular Genetic Features of Pulmonary Hypertension in Patients with Hereditary Hemorrhagic Telangiectasia
Richard C. Trembath, F.R.C.P., Jennifer R. Thomson, M.R.C.P., Rajiv D. Machado, B.Sc., Neil V. Morgan, B.Sc., Carl Atkinson, B.Sc., Ingrid Winship, M.D., Gerald Simonneau, M.D., Nazzareno Galie, M.D., James E. Loyd, M.D., Marc Humbert, M.D., William C. Nichols, Ph.D., Jonathan Berg, M.D., Alessandra Manes, M.D., Julie McGaughran, M.D., Michael Pauciulo, B.Sc., Lisa Wheeler, B.Sc., and Nicholas W. Morrell, M.D.
Background Most patients with familial primary pulmonary hypertensionhave defects in the gene for bone morphogenetic protein receptorII (BMPR2), a member of the transforming growth factor (TGF-)superfamily of receptors. Because patients with hereditary hemorrhagictelangiectasia may have lung disease that is indistinguishablefrom primary pulmonary hypertension, we investigated the geneticbasis of lung disease in these patients.
Methods We evaluated members of five kindreds plus one individualpatient with hereditary hemorrhagic telangiectasia and identified10 cases of pulmonary hypertension. In the two largest families,we used microsatellite markers to test for linkage to genesencoding TGF-receptor proteins, including endoglin andactivin-receptorlike kinase 1 (ALK1), and BMPR2. In subjectswith hereditary hemorrhagic telangiectasia and pulmonary hypertension,we also scanned ALK1 and BMPR2 for mutations.
Results We identified suggestive linkage of pulmonary hypertensionwith hereditary hemorrhagic telangiectasia on chromosome 12q13,a region that includes ALK1. We identified amino acid changesin activin-receptorlike kinase 1 that were inheritedin subjects who had a disorder with clinical and histologicfeatures indistinguishable from those of primary pulmonary hypertension.Immunohistochemical analysis in four subjects and one controlshowed pulmonary vascular endothelial expression of activin-receptorlikekinase 1 in normal and diseased pulmonary arteries.
Conclusions Pulmonary hypertension in association with hereditaryhemorrhagic telangiectasia can involve mutations in ALK1. Thesemutations are associated with diverse effects, including thevascular dilatation characteristic of hereditary hemorrhagictelangiectasia and the occlusion of small pulmonary arteriesthat is typical of primary pulmonary hypertension.
Source Information
From the Division of Medical Genetics, Departments of Medicine and Genetics, University of Leicester, Leicester, United Kingdom (R.C.T., J.R.T., R.D.M., N.V.M.); the Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke's and Papworth Hospitals, Cambridge, United Kingdom (C.A., N.W.M.); the Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand (I.W.); the Service de Pneumologie, Hôpital Antoine Béclère, Assistance PubliqueHôpitaux de Paris, Université Paris-Sud, Clamart, France (G.S., M.H.); the Institute of Cardiology, University of Bologna, Bologna, Italy (N.G.); Vanderbilt University Medical Center, Nashville (J.E.L.); and the Division of Human Genetics, Children's Hospital Medical Center, Cincinnati (W.C.N.).
Other authors were Jonathan Berg, M.D., Department of Clinical Genetics, Guy's Hospital Campus, King's College, London; Alessandra Manes, M.D., Institute of Cardiology, University of Bologna, Bologna, Italy; Julie McGaughran, M.D., Department of Molecular Medicine, School of Medicine, University of Auckland, Auckland, New Zealand; Michael Pauciulo, B.Sc., Division of Human Genetics, Children's Hospital Medical Center, Cincinnati; and Lisa Wheeler, B.Sc., Vanderbilt University Medical Center, Nashville.
Address reprint requests to Dr. Trembath at the Division of Medical Genetics, Departments of Medicine and Genetics, Adrian Bldg., University of Leicester, Leicester LE1 7RH, United Kingdom, or at rtrembat{at}hgmp.mrc.ac.uk.
Tipps, R. S., Mumtaz, M., Leahy, P., Duncan, B. W.
(2008). Gene array analysis of a rat model of pulmonary arteriovenous malformations after superior cavopulmonary anastomosis.. J. Thorac. Cardiovasc. Surg.
136: 283-289
[Abstract][Full Text]
Hoeper, M. M., Humbert, M.
(2008). A message on the lips. Eur Respir J
32: 15-16
[Full Text]
Shovlin, C. L., Tighe, H. C., Davies, R. J., Gibbs, J. S. R., Jackson, J. E.
(2008). Embolisation of pulmonary arteriovenous malformations: no consistent effect on pulmonary artery pressure. Eur Respir J
32: 162-169
[Abstract][Full Text]
Lu, Q.
(2008). Transforming growth factor-{beta}1 protects against pulmonary artery endothelial cell apoptosis via ALK5. Am. J. Physiol. Lung Cell. Mol. Physiol.
295: L123-L133
[Abstract][Full Text]
Haworth, S G
(2008). The management of pulmonary hypertension in children. Arch. Dis. Child.
93: 620-625
[Abstract][Full Text]
Ashley-Koch, A. E., Elliott, L., Kail, M. E., De Castro, L. M., Jonassaint, J., Jackson, T. L., Price, J., Ataga, K. I., Levesque, M. C., Weinberg, J. B., Orringer, E. P., Collins, A., Vance, J. M., Telen, M. J.
(2008). Identification of genetic polymorphisms associated with risk for pulmonary hypertension in sickle cell disease. Blood
111: 5721-5726
[Abstract][Full Text]
David, L., Mallet, C., Keramidas, M., Lamande, N., Gasc, J.-M., Dupuis-Girod, S., Plauchu, H., Feige, J.-J., Bailly, S.
(2008). Bone Morphogenetic Protein-9 Is a Circulating Vascular Quiescence Factor. Circ. Res.
102: 914-922
[Abstract][Full Text]
National Pulmonary Hypertension Centres of the UK,
(2008). Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Heart
94: i1-i41
[Full Text]
National Pulmonary Hypertension Centres of the UK,
(2008). Consensus statement on the management of pulmonary hypertension in clinical practice in the UK and Ireland. Thorax
63: ii1-ii41
[Full Text]
Newman, J. H., Phillips, J. A. III, Loyd, J. E.
(2008). Narrative Review: The Enigma of Pulmonary Arterial Hypertension: New Insights from Genetic Studies. ANN INTERN MED
148: 278-283
[Abstract][Full Text]
SWANSON, K. L., KROWKA, M. J.
(2008). Screen for portopulmonary hypertension, especially in liver transplant candidates. Cleveland Clinic Journal of Medicine
75: 121-136
[Abstract][Full Text]
Frank, D. B., Lowery, J., Anderson, L., Brink, M., Reese, J., de Caestecker, M.
(2008). Increased susceptibility to hypoxic pulmonary hypertension in Bmpr2 mutant mice is associated with endothelial dysfunction in the pulmonary vasculature. Am. J. Physiol. Lung Cell. Mol. Physiol.
294: L98-L109
[Abstract][Full Text]
Aldred, M. A., Machado, R. D., James, V., Morrell, N. W., Trembath, R. C.
(2007). Characterization of the BMPR2 5'-Untranslated Region and a Novel Mutation in Pulmonary Hypertension. Am. J. Respir. Crit. Care Med.
176: 819-824
[Abstract][Full Text]
Liu, D., Wang, J., Kinzel, B., Mueller, M., Mao, X., Valdez, R., Liu, Y., Li, E.
(2007). Dosage-dependent requirement of BMP type II receptor for maintenance of vascular integrity. Blood
110: 1502-1510
[Abstract][Full Text]
Tidswell, M., Higgins, T. L.
(2007). The Anesthesiologist and Pulmonary Arterial Hypertension. SEMIN CARDIOTHORAC VASC ANESTH
11: 93-95
Zakrzewicz, A., Kouri, F. M., Nejman, B., Kwapiszewska, G., Hecker, M., Sandu, R., Dony, E., Seeger, W., Schermuly, R. T., Eickelberg, O., Morty, R. E.
(2007). The transforming growth factor-{beta}/Smad2,3 signalling axis is impaired in experimental pulmonary hypertension. Eur Respir J
29: 1094-1104
[Abstract][Full Text]
Perros, F., Dorfmuller, P., Souza, R., Durand-Gasselin, I., Godot, V., Capel, F., Adnot, S., Eddahibi, S., Mazmanian, M., Fadel, E., Herve, P., Simonneau, G., Emilie, D., Humbert, M.
(2007). Fractalkine-induced smooth muscle cell proliferation in pulmonary hypertension. Eur Respir J
29: 937-943
[Abstract][Full Text]
Minai, O. A., Rigelsky, C., Eng, C., Arroliga, A. C., Stoller, J. K.
(2007). Long-term Outcome in a Patient With Pulmonary Hypertension and Hereditary Hemorrhagic Telangiectasia. Chest
131: 984-987
[Abstract][Full Text]
Gedge, F., McDonald, J., Phansalkar, A., Chou, L.-S., Calderon, F., Mao, R., Lyon, E., Bayrak-Toydemir, P.
(2007). Clinical and Analytical Sensitivities in Hereditary Hemorrhagic Telangiectasia Testing and a Report of de Novo Mutations. J. Mol. Diagn.
9: 258-265
[Abstract][Full Text]
McMurtry, M. S., Moudgil, R., Hashimoto, K., Bonnet, S., Michelakis, E. D., Archer, S. L.
(2007). Overexpression of human bone morphogenetic protein receptor 2 does not ameliorate monocrotaline pulmonary arterial hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol.
292: L872-L878
[Abstract][Full Text]
Boyer, D., Westra, S. J., Kinane, T. B., Stone, J. R.
(2007). Case 3-2007 -- A 3-Year-Old Boy with Recurrent Episodes of Respiratory Insufficiency. NEJM
356: 398-407
[Full Text]
Morrell, N. W.
(2006). Pulmonary Hypertension Due to BMPR2 Mutation: A New Paradigm for Tissue Remodeling?. Proc Am Thorac Soc
3: 680-686
[Abstract][Full Text]
Ghofrani, H. A., Voswinckel, R., Reichenberger, F., Weissmann, N., Schermuly, R. T., Seeger, W., Grimminger, F.
(2006). Hypoxia- and non-hypoxia-related pulmonary hypertension - Established and new therapies. Cardiovasc Res
72: 30-40
[Abstract][Full Text]
McLaughlin, V. V., McGoon, M. D.
(2006). Pulmonary Arterial Hypertension. Circulation
114: 1417-1431
[Full Text]
Hoeper, M. M., Rubin, L. J.
(2006). Update in pulmonary hypertension 2005.. Am. J. Respir. Crit. Care Med.
173: 499-505
[Full Text]
Fernandez-L, A., Sanz-Rodriguez, F., Blanco, F. J., Bernabeu, C., Botella, L. M.
(2006). Hereditary Hemorrhagic Telangiectasia, a Vascular Dysplasia Affecting the TGF-{beta} Signaling Pathway.. Clin Med Res
4: 66-78
[Abstract][Full Text]
Gu, Y., Jin, P., Zhang, L., Zhao, X., Gao, X., Ning, Y., Meng, A., Chen, Y.-G.
(2006). Functional analysis of mutations in the kinase domain of the TGF-beta receptor ALK1 reveals different mechanisms for induction of hereditary hemorrhagic telangiectasia. Blood
107: 1951-1954
[Abstract][Full Text]
Abdalla, S A, Letarte, M
(2006). Hereditary haemorrhagic telangiectasia: current views on genetics and mechanisms of disease. J. Med. Genet.
43: 97-110
[Abstract][Full Text]
Rubin, L. J.
(2006). Pulmonary arterial hypertension.. Proc Am Thorac Soc
3: 111-115
[Abstract][Full Text]
Mouthon, L., Guillevin, L., Humbert, M.
(2005). Pulmonary arterial hypertension: an autoimmune disease?. Eur Respir J
26: 986-988
[Full Text]
Bertolino, P., Deckers, M., Lebrin, F., ten Dijke, P.
(2005). Transforming Growth Factor-{beta} Signal Transduction in Angiogenesis and Vascular Disorders. Chest
128: 585S-590S
[Abstract][Full Text]
Bertolino, P., Deckers, M., Lebrin, F., ten Dijke, P.
(2005). Transforming Growth Factor-{beta} Signal Transduction in Angiogenesis and Vascular Disorders. Chest
128: 585S-590S
[Abstract][Full Text]
Zaiman, A., Fijalkowska, I., Hassoun, P. M., Tuder, R. M.
(2005). One Hundred Years of Research in the Pathogenesis of Pulmonary Hypertension. Am. J. Respir. Cell Mol. Bio.
33: 425-431
[Full Text]
Wong, W. K. P., Knowles, J. A., Morse, J. H.
(2005). Bone Morphogenetic Protein Receptor Type II C-Terminus Interacts with c-Src: Implication for a Role in Pulmonary Arterial Hypertension. Am. J. Respir. Cell Mol. Bio.
33: 438-446
[Abstract][Full Text]
Newman, J. H.
(2005). Pulmonary Hypertension. Am. J. Respir. Crit. Care Med.
172: 1072-1077
[Abstract][Full Text]
Tamby, M C, Chanseaud, Y, Humbert, M, Fermanian, J, Guilpain, P, Garcia-de-la-Pena-Lefebvre, P, Brunet, S, Servettaz, A, Weill, B., Simonneau, G, Guillevin, L, Boissier, M C, Mouthon, L
(2005). Anti-endothelial cell antibodies in idiopathic and systemic sclerosis associated pulmonary arterial hypertension. Thorax
60: 765-772
[Abstract][Full Text]
Adatia, I.
(2005). Improving the Outcome of Childhood Pulmonary Arterial Hypertension: The Effect of Bosentan in the Setting of a Dedicated Pulmonary Hypertension Clinic. J Am Coll Cardiol
46: 705-706
[Full Text]
Cole, S G, Begbie, M E, Wallace, G M F, Shovlin, C L
(2005). A new locus for hereditary haemorrhagic telangiectasia (HHT3) maps to chromosome 5. J. Med. Genet.
42: 577-582
[Abstract][Full Text]
Herrick, A. L.
(2005). Pathogenesis of Raynaud's phenomenon. Rheumatology (Oxford)
44: 587-596
[Abstract][Full Text]
Harrison, R. E., Berger, R., Haworth, S. G., Tulloh, R., Mache, C. J., Morrell, N. W., Aldred, M. A., Trembath, R. C.
(2005). Transforming Growth Factor-{beta} Receptor Mutations and Pulmonary Arterial Hypertension in Childhood. Circulation
111: 435-441
[Abstract][Full Text]
Satoh, T., Kimura, K., Okano, Y., Hirakata, M., Kawakami, Y., Kuwana, M.
(2005). Lack of circulating autoantibodies to bone morphogenetic protein receptor-II or activin receptor-like kinase 1 in mixed connective tissue disease patients with pulmonary arterial hypertension. Rheumatology (Oxford)
44: 192-196
[Abstract][Full Text]
Task Force members, , Galie, N., Torbicki, A., Barst, R., Dartevelle, P., Haworth, S., Higenbottam, T., Olschewski, H., Peacock, A., Pietra, G., Rubin, L. J., Simonneau, G.
(2004). Guidelines on diagnosis and treatment of pulmonary arterial hypertension: The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J
25: 2243-2278
[Full Text]
Beppu, H., Ichinose, F., Kawai, N., Jones, R. C., Yu, P. B., Zapol, W. M., Miyazono, K., Li, E., Bloch, K. D.
(2004). BMPR-II heterozygous mice have mild pulmonary hypertension and an impaired pulmonary vascular remodeling response to prolonged hypoxia. Am. J. Physiol. Lung Cell. Mol. Physiol.
287: L1241-L1247
[Abstract][Full Text]
Rodriguez-Roisin, R., Krowka, M.J., Herve, Ph., Fallon, M.B., on behalf of the ERS Task Force Pulmonary-Hepatic,
(2004). Pulmonary-Hepatic vascular Disorders (PHD). Eur Respir J
24: 861-880
[Full Text]
Farber, H. W., Loscalzo, J.
(2004). Pulmonary Arterial Hypertension. NEJM
351: 1655-1665
[Full Text]
Takeda, M., Otsuka, F., Nakamura, K., Inagaki, K., Suzuki, J., Miura, D., Fujio, H., Matsubara, H., Date, H., Ohe, T., Makino, H.
(2004). Characterization of the Bone Morphogenetic Protein (BMP) System in Human Pulmonary Arterial Smooth Muscle Cells Isolated from a Sporadic Case of Primary Pulmonary Hypertension: Roles of BMP Type IB Receptor (Activin Receptor-Like Kinase-6) in the Mitotic Action. Endocrinology
145: 4344-4354
[Abstract][Full Text]
Doherty, T. M., Fitzpatrick, L. A., Inoue, D., Qiao, J.-H., Fishbein, M. C., Detrano, R. C., Shah, P. K., Rajavashisth, T. B.
(2004). Molecular, Endocrine, and Genetic Mechanisms of Arterial Calcification. Endocr. Rev.
25: 629-672
[Abstract][Full Text]
McGoon, M., Gutterman, D., Steen, V., Barst, R., McCrory, D. C., Fortin, T. A., Loyd, J. E.
(2004). Screening, Early Detection, and Diagnosis of Pulmonary Arterial Hypertension: ACCP Evidence-Based Clinical Practice Guidelines. Chest
126: 14S-34S
[Abstract][Full Text]
Newman, J. H., Fanburg, B. L., Archer, S. L., Badesch, D. B., Barst, R. J., Garcia, J. G.N., Kao, P. N., Knowles, J. A., Loyd, J. E., McGoon, M. D., Morse, J. H., Nichols, W. C., Rabinovitch, M., Rodman, D. M., Stevens, T., Tuder, R. M., Voelkel, N. F., Gail, D. B.
(2004). Pulmonary Arterial Hypertension: Future Directions: Report of a National Heart, Lung and Blood Institute/Office of Rare Diseases Workshop. Circulation
109: 2947-2952
[Full Text]
Simonneau, G., Galie, N., Rubin, L. J., Langleben, D., Seeger, W., Domenighetti, G., Gibbs, S., Lebrec, D., Speich, R., Beghetti, M., Rich, S., Fishman, A.
(2004). Clinical classification of pulmonary hypertension. J Am Coll Cardiol
43: 5S-12S
[Abstract][Full Text]
Humbert, M., Morrell, N. W., Archer, S. L., Stenmark, K. R., MacLean, M. R., Lang, I. M., Christman, B. W., Weir, E. K., Eickelberg, O., Voelkel, N. F., Rabinovitch, M.
(2004). Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol
43: 13S-24S
[Abstract][Full Text]
Newman, J. H., Trembath, R. C., Morse, J. A., Grunig, E., Loyd, J. E., Adnot, S., Coccolo, F., Ventura, C., Phillips, J. A. III, Knowles, J. A., Janssen, B., Eickelberg, O., Eddahibi, S., Herve, P., Nichols, W. C., Elliott, G.
(2004). Genetic basis of pulmonary arterial hypertension: Current understanding and future directions. J Am Coll Cardiol
43: 33S-39S
[Abstract][Full Text]
Chaouat, A, Coulet, F, Favre, C, Simonneau, G, Weitzenblum, E, Soubrier, F, Humbert, M
(2004). Endoglin germline mutation in a patient with hereditary haemorrhagic telangiectasia and dexfenfluramine associated pulmonary arterial hypertension. Thorax
59: 446-448
[Abstract][Full Text]
Jones, J. E., Walker, J. L., Song, Y., Weiss, N., Cardoso, W. V., Tuder, R. M., Loscalzo, J., Zhang, Y.-Y.
(2004). Effect of 5-lipoxygenase on the development of pulmonary hypertension in rats. Am. J. Physiol. Heart Circ. Physiol.
286: H1775-H1784
[Abstract][Full Text]
Budhiraja, R., Tuder, R. M., Hassoun, P. M.
(2004). Endothelial Dysfunction in Pulmonary Hypertension. Circulation
109: 159-165
[Full Text]
Harrison, R E, Flanagan, J A, Sankelo, M, Abdalla, S A, Rowell, J, Machado, R D, Elliott, C G, Robbins, I M, Olschewski, H, McLaughlin, V, Gruenig, E, Kermeen, F, Laitinen, T, Morrell, N W, Trembath, R C
(2003). Molecular and functional analysis identifies ALK-1 as the predominant cause of pulmonary hypertension related to hereditary haemorrhagic telangiectasia. J. Med. Genet.
40: 865-871
[Abstract][Full Text]
Dorfmuller, P., Perros, F., Balabanian, K., Humbert, M.
(2003). Inflammation in pulmonary arterial hypertension. Eur Respir J
22: 358-363
[Abstract][Full Text]
Abdalla, S A, Geisthoff, U W, Bonneau, D, Plauchu, H, McDonald, J, Kennedy, S, Faughnan, M E, Letarte, M
(2003). Visceral manifestations in hereditary haemorrhagic telangiectasia type 2. J. Med. Genet.
40: 494-502
[Abstract][Full Text]
Mata-Greenwood, E., Meyrick, B., Steinhorn, R. H., Fineman, J. R., Black, S. M.
(2003). Alterations in TGF-{beta}1 expression in lambs with increased pulmonary blood flow and pulmonary hypertension. Am. J. Physiol. Lung Cell. Mol. Physiol.
285: L209-L221
[Abstract][Full Text]
Rindermann, M., Grunig, E., von Hippel, A., Koehler, R., Miltenberger-Miltenyi, G., Mereles, D., Arnold, K., Pauciulo, M., Nichols, W., Olschewski, H., Hoeper, M. M., Winkler, J.o., Katus, H. A., Kubler, W., Bartram, C. R., Janssen, B.
(2003). Primary pulmonary hypertension may be a heterogeneous disease with a second locus on chromosome 2q31. J Am Coll Cardiol
41: 2237-2244
[Abstract][Full Text]
Marchuk, D. A., Srinivasan, S., Squire, T. L., Zawistowski, J. S.
(2003). Vascular morphogenesis: tales of two syndromes. Hum Mol Genet
12: R97-112
[Abstract][Full Text]
van den Driesche, S., Mummery, C. L., Westermann, C. J.J.
(2003). Hereditary hemorrhagic telangiectasia: an update on transforming growth factor {beta} signaling in vasculogenesis and angiogenesis. Cardiovasc Res
58: 20-31
[Abstract][Full Text]
Runo, J. R., Vnencak-Jones, C. L., Prince, M., Loyd, J. E., Wheeler, L., Robbins, I. M., Lane, K. B., Newman, J. H., Johnson, J., Nichols, W. C., Phillips, J. A. III
(2003). Pulmonary Veno-occlusive Disease Caused by an Inherited Mutation in Bone Morphogenetic Protein Receptor II. Am. J. Respir. Crit. Care Med.
167: 889-894
[Abstract][Full Text]
Srinivasan, S., Hanes, M. A., Dickens, T., Porteous, M. E. M., Oh, S. P., Hale, L. P., Marchuk, D. A.
(2003). A mouse model for hereditary hemorrhagic telangiectasia (HHT) type 2. Hum Mol Genet
12: 473-482
[Abstract][Full Text]
Morse, J H
(2003). Genetic studies of pulmonary arterial hypertension. Lupus
12: 209-212
[Abstract]
Du, L., Sullivan, C. C., Chu, D., Cho, A. J., Kido, M., Wolf, P. L., Yuan, J. X.-J., Deutsch, R., Jamieson, S. W., Thistlethwaite, P. A.
(2003). Signaling Molecules in Nonfamilial Pulmonary Hypertension. NEJM
348: 500-509
[Abstract][Full Text]
Begbie, M E, Wallace, G M F, Shovlin, C L
(2003). Hereditary haemorrhagic telangiectasia (Osler-Weber-Rendu syndrome): a view from the 21st century. Postgrad. Med. J.
79: 18-24
[Abstract][Full Text]
Lamouille, S., Mallet, C., Feige, J.-J., Bailly, S.
(2002). Activin receptor-like kinase 1 is implicated in the maturation phase of angiogenesis. Blood
100: 4495-4501
[Abstract][Full Text]
Eddahibi, S., Morrell, N., d'Ortho, M-P., Naeije, R., Adnot, S.
(2002). Pathobiology of pulmonary arterial hypertension. Eur Respir J
20: 1559-1572
[Abstract][Full Text]
Loyd, J. E.
(2002). Genetics and Pulmonary Hypertension. Chest
122: 284S-286S
[Abstract][Full Text]
Humbert, M., Trembath, R.C.
(2002). Genetics of pulmonary hypertension: from bench to bedside. Eur Respir J
20: 741-749
[Abstract][Full Text]
Harris, S.E., Chand, A.L., Winship, I.M., Gersak, K., Aittomaki, K., Shelling, A.N.
(2002). Identification of novel mutations in FOXL2 associated with premature ovarian failure. Mol Hum Reprod
8: 729-733
[Abstract][Full Text]
Humbert, M., Labrune, P., Sitbon, O., Le Gall, C., Callebert, J., Herve, P., Samuel, D., Machado, R., Trembath, R., Drouet, L., Launay, J-M., Simonneau, G.
(2002). Pulmonary arterial hypertension and type-I glycogen-storage disease: the serotonin hypothesis. Eur Respir J
20: 59-65
[Abstract][Full Text]
Olivieri, C, Mira, E, Delu, G, Pagella, F, Zambelli, A, Malvezzi, L, Buscarini, E, Danesino, C
(2002). Identification of 13 new mutations in the ACVRL1 gene in a group of 52 unselected Italian patients affected by hereditary haemorrhagic telangiectasia. J. Med. Genet.
39: e39-39
[Full Text]
Balabanian, K., Foussat, A., Dorfmuller, P., Durand-Gasselin, I., Capel, F., Bouchet-Delbos, L., Portier, A., Marfaing-Koka, A., Krzysiek, R., Rimaniol, A.-C., Simonneau, G., Emilie, D., Humbert, M.
(2002). CX3C Chemokine Fractalkine in Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med.
165: 1419-1425
[Abstract][Full Text]
Newman, J. H.
(2002). Treatment of Primary Pulmonary Hypertension -- The Next Generation. NEJM
346: 933-935
[Full Text]
Morse, J. H.
(2002). Bone Morphogenetic Protein Receptor 2 Mutations in Pulmonary Hypertension. Chest
121: 50S-53S
[Abstract][Full Text]
DORFMULLER, P., ZARKA, V., DURAND-GASSELIN, I., MONTI, G., BALABANIAN, K., GARCIA, G., CAPRON, F., COULOMB-LHERMINE, A., MARFAING-KOKA, A., SIMONNEAU, G., EMILIE, D., HUMBERT, M.
(2002). Chemokine RANTES in Severe Pulmonary Arterial Hypertension. Am. J. Respir. Crit. Care Med.
165: 534-539
[Abstract][Full Text]
Rudarakanchana, N, Trembath, R C, Morrell, N W
(2001). New insights into the pathogenesis and treatment of primary pulmonary hypertension. Thorax
56: 888-890
[Full Text]
Loscalzo, J.
(2001). Genetic Clues to the Cause of Primary Pulmonary Hypertension. NEJM
345: 367-371
[Full Text]
Welch, C. A.
(2001). Sacred Secrets -- The Privacy of Medical Records. NEJM
345: 371-372
[Full Text]