Transforming growth factor-beta receptor mutations and pulmonary arterial hypertension in childhood.
Circulation
; 111(4): 435-41, 2005 Feb 01.
Article
em En
| MEDLINE
| ID: mdl-15687131
ABSTRACT
BACKGROUND:
Pulmonary arterial hypertension (PAH) is a potentially fatal vasculopathy that can develop at any age. Adult-onset disease has previously been associated with mutations in BMPR2 and ALK-1. Presentation in early life may be associated with congenital heart disease but frequently is idiopathic. METHODS ANDRESULTS:
We performed mutation analysis in genes encoding receptor members of the transforming growth factor-beta cell-signaling pathway in 18 children (age at presentation <6 years) with PAH. Sixteen children were initially diagnosed with idiopathic PAH and 2 with PAH in association with congenital heart defects. Germ-line mutations were observed in 4 patients (22%) (age at disease onset, 1 month to 6 years), all of whom presented with idiopathic PAH. The BMPR2 mutations (n=2, 11%) included a partial gene deletion and a nonsense mutation, both arising de novo in the proband. Importantly, a missense mutation of ALK-1 and a branch-site mutation of endoglin were also detected. Presenting clinical features or progression of pulmonary hypertension did not distinguish between patients with mutations in the different genes or between those without mutations.CONCLUSIONS:
The cause of PAH presenting in childhood is heterogeneous in nature, with genetic defects of transforming growth factor-beta receptors playing a critical role.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transdução de Sinais
/
Fator de Crescimento Transformador beta
/
Proteínas Serina-Treonina Quinases
/
Receptores de Fatores de Crescimento Transformadores beta
/
Molécula 1 de Adesão de Célula Vascular
/
Receptores de Ativinas Tipo I
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Hipertensão Pulmonar
Tipo de estudo:
Etiology_studies
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article