title: Pulmonary Vasculopathy Associated with FIGF Gene Mutation.
abstract: 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.
authors.affiliation: Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Evan
authors.initials: E
authors.lastname: Bailey
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Ye
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Division of Pulmonary Medicine, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Alicia
authors.initials: A
authors.lastname: Casey
authors.affiliation: Division of Genetics and Genomics, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Joan M
authors.initials: JM
authors.lastname: Stoler
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Xingbin
authors.initials: X
authors.lastname: Ai
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Ma
authors.affiliation: Division of Hematology, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Robert
authors.initials: R
authors.lastname: Handin
authors.affiliation: Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts.
authors.forename: Piotr
authors.initials: P
authors.lastname: Sliz
authors.affiliation: Department of Pathology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
authors.forename: Sara O
authors.initials: SO
authors.lastname: Vargas
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts. Electronic address: sel-chemaly@partners.org.
authors.forename: Souheil Y
authors.initials: SY
authors.lastname: El-Chemaly
mesh_terms: D000818:Animals; D002460:Cell Line; D002645:Chickens; D002648:Child; D002675:Child, Preschool; D005190:Family; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008168:Lung / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D008171:Lung Diseases / Q000097:blood / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D009389:Neovascularization, Pathologic / Q000235:genetics; D014652:Vascular Diseases / Q000097:blood / Q000235:genetics*; D042643:Vascular Endothelial Growth Factor D / Q000097:blood / Q000235:genetics* / Q000378:metabolism
chemical_list: C579459:VEGFD protein, human; D042643:Vascular Endothelial Growth Factor D