Abstract | RATIONALE: OBJECTIVES: To describe the characteristics of patients with PAH carrying an ACVRL1 mutation. METHODS: We reviewed clinical, functional, and hemodynamic characteristics of 32 patients with PAH carrying an ACVRL1 mutation, corresponding to 9 patients from the French PAH Network and 23 from literature analysis. These cases were compared with 370 patients from the French PAH Network (93 with a bone morphogenetic protein receptor type 2 [BMPR2] mutation and 277 considered as idiopathic cases without identified mutation). Distribution of mutations in the ACVRL1 gene in patients with PAH was compared with the HHT Mutation Database. MEASUREMENTS AND MAIN RESULTS: At diagnosis, ACVRL1 mutation carriers were significantly younger (21.8 +/- 16.7 yr) than BMPR2 mutation carriers and noncarriers (35.7 +/- 14.9 and 47.6 +/- 16.3 yr, respectively; P < 0.0001). In seven of the nine patients from the French PAH Network, PAH diagnosis preceded manifestations of HHT. ACVRL1 mutation carriers had better hemodynamic status at diagnosis, but none responded to acute vasodilator challenge and they had shorter survival when compared with other patients with PAH despite similar use of specific therapies. ACVRL1 mutations in exon 10 were more frequently observed in patients with PAH, as compared with what was observed in the HHT Mutation Database (33.3 vs. 5%; P < 0.0001). CONCLUSIONS: ACVRL1 mutation carriers were characterized by a younger age at PAH diagnosis. Despite less severe initial hemodynamics and similar management, these patients had worse prognosis compared with other patients with PAH, suggesting more rapid disease progression.
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Authors | Barbara Girerd, David Montani, Florence Coulet, Benjamin Sztrymf, Azzeddine Yaici, Xavier Jaïs, David Tregouet, Abilio Reis, Valérie Drouin-Garraud, Alain Fraisse, Olivier Sitbon, Dermot S O'Callaghan, Gérald Simonneau, Florent Soubrier, Marc Humbert |
Journal | American journal of respiratory and critical care medicine
(Am J Respir Crit Care Med)
Vol. 181
Issue 8
Pg. 851-61
(Apr 15 2010)
ISSN: 1535-4970 [Electronic] United States |
PMID | 20056902
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- ACVRL1 protein, human
- Activin Receptors, Type II
- BMPR2 protein, human
- Bone Morphogenetic Protein Receptors, Type II
- Oxygen
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Topics |
- Activin Receptors, Type II
(genetics)
- Adolescent
- Adult
- Age Distribution
- Blood Pressure
- Bone Morphogenetic Protein Receptors, Type II
(genetics)
- Child
- Child, Preschool
- Exercise Test
(methods, statistics & numerical data)
- Female
- France
- Humans
- Hypertension, Pulmonary
(genetics, physiopathology)
- Infant
- Male
- Middle Aged
- Oxygen
(blood)
- Point Mutation
(genetics)
- Pulmonary Artery
- Pulmonary Wedge Pressure
- Registries
- Sequence Deletion
(genetics)
- Survival Analysis
- Vascular Resistance
- Young Adult
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