PT  - JOURNAL ARTICLE
AU  - M. Humbert
AU  - Z. Deng
AU  - G. Simonneau
AU  - R.J. Barst
AU  - O. Sitbon
AU  - M. Wolf
AU  - N. Cuervo
AU  - K.J. Moore
AU  - S.E. Hodge
AU  - J.A. Knowles
AU  - J.H. Morse
TI  - BMPR2 germline mutations in pulmonary hypertension associated with fenfluramine derivatives
AID  - 10.1183/09031936.02.01762002
DP  - 2002 Sep 01
TA  - European Respiratory Journal
PG  - 518--523
VI  - 20
IP  - 3
4099  - http://erj.ersjournals.com/content/20/3/518.short
4100  - http://erj.ersjournals.com/content/20/3/518.full
SO  - Eur Respir J2002 Sep 01; 20
AB  - This study investigated whether patients developing pulmonary arterial hypertension (PAH) after exposure to the appetite suppressants fenfluramine and dexfenfluramine have mutations in the bone morphogenetic protein receptor 2 (BMPR2) gene, as reported in primary pulmonary hypertension. BMPR2 was examined for mutations in 33 unrelated patients with sporadic PAH, and in two sisters with PAH, all of whom had taken fenfluramine derivatives, as well as in 130 normal controls. The PAH patients also underwent cardiac catheterisation and body mass determinations. Three BMPR2 mutations predicting changes in the primary structure of the BMPR-II protein were found in three of the 33 unrelated patients (9%), and a fourth mutation was found in the two sisters. No BMPR2 mutations were identified in the 130 normal controls. This difference in frequency was statistically significant. Moreover, the mutation-positive patients had a somewhat shorter duration of fenfluramine exposure before illness than the mutation-negative patients, a difference that was statistically significant when the two sisters were included in the analysis. In conclusion, the present authors have detected bone morphogenetic protein receptor 2 mutations that appear to be rare in the general population but may combine with exposure to fenfluramine derivatives to greatly increase the risk of developing severe pulmonary arterial hypertension. This study was supported by grants from NIH-HBLI-60056, NIH-DK-31813, INSERM, AFM, and Université Paris-Sud. Z. Deng was supported by a PHA fellowship award.