Neonatal Pulmonary Arterial Hypertension and Noonan Syndrome: Two Fatal Cases with a Specific RAF1 Mutation

作者：Hopper Rachel K; Feinstein Jeffrey A; Manning Melanie A; Benitz William; Hudgins Louanne^*

来源：American Journal of Medical Genetics, Part A, 2015, 167(4): 882-885.

DOI：10.1002/ajmg.a.37024

• Noonan syndrome
• pulmonary arterial hypertension
• Raf-1

Mutations in RAF1 are associated with Noonan syndrome and hypertrophic cardiomyopathy. We present two infants with Noonan syndrome and an identical RAF1 mutation, p.Ser257Leu (c.770C>T), who developed severe pulmonary arterial hypertension (PAH) that proved to be fatal. The RAF1 gene encodes Raf-1 kinase, part of the Ras/mitogen-activated kinase (MAPK) signaling pathway, which has been linked to the development of PAH. This specific mutation has been associated with dephosphorylation of a critical serine residue and constitutive activation of the Raf-1 kinase. These two cases suggest that abnormal activation of the Ras/MAPK pathway may play a significant role in the development of pulmonary vascular disease in the subset of patients with Noonan syndrome and a specific RAF1 mutation.

• 出版日期2015-4