Vasculopathy in two cases of NF1-related congenital pseudarthrosis.
Neurofibromatosis type 1 (NF1) is a common dominantly inherited disease. More than half of NF1 patients suffer from skeletal manifestations, of which congenital pseudarthrosis of tibia (CPT) is one of the most incapacitating lesions. Two NF1 patients with CPT were operated, and the resected tissues were analyzed using immunohistochemistry and/or in situ hybridization for NF1 protein and mRNA, p-p44/42 MAPK, and S100 protein. Both patients displayed thick-walled arteries and veins with a small lumen within the fibrotic tissue in the vicinity of pseudarthrosis. Endothelial cells were highly positive for p-p44/42 MAPK. A subpopulation of cells surrounding the blood vessels was S100 protein-positive. However, the exact identity of the S100-positive cells remains to be elucidated. Neurofibromin mRNA and protein labeling was detected in both cell types. In conclusion, decreased NF1 function as a RAS-GAP in the endothelium may contribute to vascular thickening in CPT.
Kuorilehto
Tommi
T
Department of Anatomy, Institute of Biomedicine, University of Turku, Kiinanmyllynkatu, Turku, Finland.
Kinnunen
Pentti
P
Nissinen
Marja
M
Alanne
Maria
M
Leskelä
Hannu-Ville
HV
Lehenkari
Petri
P
Peltonen
Juha
J
D001808:Blood Vessels / Q000473:pathology*; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009456:Neurofibromatosis 1 / Q000150:complications*; D025542:Neurofibromin 1 / Q000378:metabolism; D011542:Pseudarthrosis / Q000150:complications / Q000151:congenital* / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis; D009418:S100 Proteins / Q000378:metabolism; D013977:Tibia / Q000098:blood supply* / Q000473:pathology* / Q000601:surgery
D025542:Neurofibromin 1; D012333:RNA, Messenger; D009418:S100 Proteins; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3