Circulation Journal
Online ISSN : 1347-4820
Print ISSN : 1346-9843
ISSN-L : 1346-9843
Clinical Investigation
Implications of Mutations of Activin Receptor-Like Kinase 1 Gene (ALK1) in Addition to Bone Morphogenetic Protein Receptor II Gene (BMPR2) in Children With Pulmonary Arterial Hypertension
Maya FujiwaraHisato YagiRumiko MatsuokaKaoru AkimotoMichiko FurutaniShin-ichiro ImamuraRitei UeharaTomotaka NakayamaAtsuyoshi TakaoMakoto NakazawaTsutomu Saji
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2008 Volume 72 Issue 1 Pages 127-133


Background Mutations of the bone morphogenetic protein receptor II gene (BMPR2), and 1 mutation of the activin receptor-like kinase 1 gene (ALK1) have been reported in patients with pulmonary arterial hypertension (PAH). Methods and Results A genomic study of ALK1 and BMPR2 was conducted in 21 PAH probands under 16 years of age to study the relationship between the clinical features of the patients and these genes. In all 4 familial aggregates of PAH, 3 ALK1 or 1 BMPR2 mutations were identified. Among 17 probands aged between 4 and 14 years with idiopathic PAH, 2 ALK1 mutations (2/17: 11.8%) and 3 BMPR2 mutations (3/17: 17.6%; 5 mutations in total: 5/17: 29.4%) were found. Conclusion Each proband with the ALK1 mutation developed PAH, as did the probands with the BMPR2 mutation. Hence, it is proposed that ALK1 plays as notable a role as BMPR2 in the etiology of PAH. Furthermore, asymptomatic carriers with the ALK1 mutation within the serine - threonine kinase domain are at risk of developing PAH and hereditary hemorrhagic telangiectasia, so close follow-up is recommended for those individuals. (Circ J 2008; 72: 127 - 133)

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