Pulmonary Vasculopathy Associated with FIGF Gene Mutation

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• 作者：Evan Bailey^&lowast ; ; Ye Cui^&dagger ; ; Alicia Casey^&lowast ; ; Joan M. Stoler^&Dagger ; ; Xingbin Ai^&dagger ; ; Dongdong Ma^§ ; ; Robert Handin^§ ; ; Piotr Sliz^¶ ; ; Sara O. Vargas^‖ ; Souheil Y. El-Chemaly^&dagger ; ; ^{sel-chemaly@partners.org}
• 刊名：The American Journal of Pathology
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：187
• 期：1
• 页码：25-32
• 全文大小：2829 K
• 卷排序：187

文摘

Vascular endothelial growth factor (VEGF)-D is capable of inducing angiogenesis and lymphangiogenesis through signaling via VEGF receptor (VEGFR)-2 and VEGFR-3, respectively. Mutations in the FIGF (c-fos–induced growth factor) gene encoding VEGF-D have not been reported previously. We describe a young male with a hemizygous mutation in the X-chromosome gene FIGF (c.352 G>A) associated with early childhood respiratory deficiency. Histologically, lungs showed ectatic pulmonary arteries and pulmonary veins. The mutation resulted in a substitution of valine to methionine at residue 118 of the VEGF-D protein. The resultant mutant protein had increased dimerization, induced elevated VEGFR-2 signaling, and caused aberrant angiogenesis in vivo. Our observations characterize a new subtype of congenital diffuse lung disease, provide a histological correlate, and support a critical role for VEGF-D in lung vascular development and homeostasis.