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Copyright ©ERS Journals Ltd 2004
Primary pulmonary hypertension in families with hereditary haemorrhagic telangiectasia
1 Cancer Research Program, Hospital for Sick Children and University of Toronto, and Heart and Stroke/Richard Lewar Centre of Excellence, University of Toronto, Toronto, Canada. 2 Dept of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, USA. Depts of 3 Pediatrics, 4 Medicine, and 5 Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA
CORRESPONDENCE: J.H. Morse, Columbia University College of Physicians and Surgeons, Dept of Medicine, New York, USA. Fax: 1 2123054943. E-mail: jhm4@columbia.edu
Keywords: pulmonary hypertension, transforming growth factor-ß, vascular disorder
Received: July 23, 2003
Accepted October 9, 2003
This study was supported by grant HHT-FY02-226 (M. Letarte) from the March of Dimes (New York, NY, USA), and by grants NIH-HL60056 (J.H. Morse) from Columbia University (New York, NY, USA) and NIH-HL49171 (D.A. Marchuk) from Duke University (Durham, NC, USA).
Primary pulmonary hypertension (PPH) is a rare but severe and progressive disease characterised by obstructive lesions of small pulmonary arteries. Patients with PPH often have mutations in the bone morphogenetic protein receptor type II (BMPR2) gene, whereas some carry mutations in the activin receptor-like kinase 1 (ALK-1) gene, generally associated with hereditary haemorrhagic telangiectasia (HHT) type 2, a vascular dysplasia affecting multiple organs. The aim of this study was to determine whether members of families with PPH and confirmed or probable HHT had ALK-1 mutations.
ALK-1 and BMPR2 mutation analysis was performed on deoxyribonucleic acid from affected members of four families with PPH and confirmed or suspected HHT.
ALK-1 mutations were identified in all four families and three novel mutations found in exon 10, leading to truncated proteins. In the fourth family, a missense mutation, previously reported in four independent HHT families, was detected in exon 8. Analysis of the BMPR2 gene revealed no exonic mutations in the probands with both PPH and HHT.
The present data bring to 10 the number of reported families with primary pulmonary hypertension and hereditary haemorrhagic telangiectasia type 2, representing 16% of the 61 families with known activin receptor-like kinase 1 mutations. Such mutations might predispose to primary pulmonary hypertension, and specialists should be aware of the potential link between these two disorders.
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