RT Journal Article
SR Electronic
T1 Primary pulmonary hypertension in families with hereditary haemorrhagic telangiectasia
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 373
OP 377
DO 10.1183/09031936.04.00085504
VO 23
IS 3
A1 S.A. Abdalla
A1 C.J. Gallione
A1 R.J. Barst
A1 E.M. Horn
A1 J.A. Knowles
A1 D.A. Marchuk
A1 M. Letarte
A1 J.H. Morse
YR 2004
UL http://erj.ersjournals.com/content/23/3/373.abstract
AB 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. 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).