Abdalla S A, Gallione C J, Barst R J, Horn E M, Knowles J A, Marchuk D A, Letarte M, Morse J H
Cancer Research Program, Hospital for Sick Children and University of Toronto, Toronto, Canada.
Eur Respir J. 2004 Mar;23(3):373-7. doi: 10.1183/09031936.04.00085504.
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.
原发性肺动脉高压（PPH）是一种罕见但严重且呈进行性发展的疾病，其特征为小肺动脉的阻塞性病变。PPH患者常伴有骨形态发生蛋白受体II型（BMPR2）基因突变，而部分患者携带激活素受体样激酶1（ALK-1）基因突变，这通常与遗传性出血性毛细血管扩张症（HHT）2型相关，HHT2型是一种影响多个器官的血管发育异常疾病。本研究的目的是确定PPH家族中确诊或疑似患有HHT的成员是否存在ALK-1基因突变。对4个患有PPH且确诊或疑似患有HHT的家族中受影响成员的脱氧核糖核酸进行了ALK-1和BMPR2基因突变分析。在所有4个家族中均检测到ALK-1基因突变，在第10外显子中发现了3个新的突变，这些突变导致蛋白质截短。在第4个家族中，在第8外显子中检测到一个错义突变，该突变先前在4个独立的HHT家族中报道过。对BMPR2基因的分析显示，同时患有PPH和HHT的先证者中未发现外显子突变。目前的数据使报道的原发性肺动脉高压合并遗传性出血性毛细血管扩张症2型的家族数量增加到10个，占已知激活素受体样激酶1基因突变的61个家族中的16%。此类突变可能易引发原发性肺动脉高压，专家应意识到这两种疾病之间的潜在联系。
