Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Mais filtros











Base de dados
Intervalo de ano de publicação
1.
J Pediatr ; 166(4): 1048-54.e1-5, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25681199

RESUMO

OBJECTIVES: To test the hypothesis that somatic phosphatidylinositol-4,5-bisphospate 3-kinase, catalytic subunit alpha (PIK3CA) mutations would be found in patients with more common disorders including isolated lymphatic malformation (LM) and Klippel-Trenaunay syndrome (KTS). STUDY DESIGN: We used next generation sequencing, droplet digital polymerase chain reaction, and single molecule molecular inversion probes to search for somatic PIK3CA mutations in affected tissue from patients seen at Boston Children's Hospital who had an isolated LM (n = 17), KTS (n = 21), fibro-adipose vascular anomaly (n = 8), or congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (n = 33), the disorder for which we first identified somatic PIK3CA mutations. We also screened 5 of the more common PIK3CA mutations in a second cohort of patients with LM (n = 31) from Seattle Children's Hospital. RESULTS: Most individuals from Boston Children's Hospital who had isolated LM (16/17) or LM as part of a syndrome, such as KTS (19/21), fibro-adipose vascular anomaly (5/8), and congenital lipomatous overgrowth with vascular, epidermal, and skeletal anomalies syndrome (31/33) were somatic mosaic for PIK3CA mutations, with 5 specific PIK3CA mutations accounting for ∼ 80% of cases. Seventy-four percent of patients with LM from Seattle Children's Hospital also were somatic mosaic for 1 of 5 specific PIK3CA mutations. Many affected tissue specimens from both cohorts contained fewer than 10% mutant cells. CONCLUSIONS: Somatic PIK3CA mutations are the most common cause of isolated LMs and disorders in which LM is a component feature. Five PIK3CA mutations account for most cases. The search for causal mutations requires sampling of affected tissues and techniques that are capable of detecting low-level somatic mosaicism because the abundance of mutant cells in a malformed tissue can be low.


Assuntos
Anormalidades Múltiplas , DNA/genética , Síndrome de Klippel-Trenaunay-Weber/genética , Anormalidades Linfáticas/genética , Mutação , Fosfatidilinositol 3-Quinases/genética , Malformações Vasculares/genética , Criança , Pré-Escolar , Classe I de Fosfatidilinositol 3-Quinases , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Lactente , Síndrome de Klippel-Trenaunay-Weber/diagnóstico , Síndrome de Klippel-Trenaunay-Weber/metabolismo , Anormalidades Linfáticas/diagnóstico , Anormalidades Linfáticas/metabolismo , Masculino , Fosfatidilinositol 3-Quinases/metabolismo , Reação em Cadeia da Polimerase , Malformações Vasculares/diagnóstico , Malformações Vasculares/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA