Double inactivation of NF1 in tibial pseudarthrosis.

Osseous abnormalities, including long-bone dysplasia with pseudarthrosis (PA), are associated with neurofibromatosis type 1 (NF1). Prospectively acquired tissue from the PA site of two individuals with NF1 was used for immunohistochemical characterization and genotype analysis of the NF1 locus. Typical immunohistochemical features of neurofibroma were not observed. Genotype analysis of PA tissue with use of four genetic markers (D17S1863, GXALU, IN38, and 3NF1-1) spanning the NF1 locus demonstrated loss of heterozygosity. These results are the first to document double inactivation of NF1 in PA tissue and suggest that the neurofibromin-Ras signal transduction pathway is involved in this bone dysplasia in NF1.

[1]  T. Kuorilehto,et al.  NF1 Gene Expression in Mouse Fracture Healing and in Experimental Rat Pseudarthrosis , 2006, The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society.

[2]  E. Everett,et al.  Neurofibromin and its inactivation of Ras are prerequisites for osteoblast functioning. , 2005, Bone.

[3]  X. Estivill,et al.  A highly informative CA/GT repeat polymorphism in intron 38 of the human neurofibromatosis type 1 (NF1) gene , 1993, Human Genetics.

[4]  J. Koivunen,et al.  NF1 Tumor Suppressor Protein and mRNA in Skeletal Tissues of Developing and Adult Normal Mouse and NF1‐Deficient Embryos , 2004, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[5]  M. Blauth,et al.  Light- and electron-microscopic studies in congenital pseudarthrosis , 2004, Archives of orthopaedic and traumatic surgery.

[6]  S. Colman,et al.  Chromosome 17 loss‐of‐heterozygosity studies in benign and malignant tumors in neurofibromatosis type 1 , 2000, Genes, chromosomes & cancer.

[7]  G Mortier,et al.  Exhaustive mutation analysis of the NF1 gene allows identification of 95% of mutations and reveals a high frequency of unusual splicing defects , 2000, Human mutation.

[8]  D. Atar,et al.  Congenital Pseudoarthrosis of the Tibia , 2000, Journal of pediatric orthopedics. Part B.

[9]  S. Wientroub,et al.  Congenital Pseudarthrosis of the Tibia: History, Etiology, Classification, and Epidemiologic Data , 2000, Journal of pediatric orthopedics. Part B.

[10]  S. Wientroub,et al.  Pathology of Bone Lesions Associated With Congenital Pseudarthrosis of the Leg , 2000, Journal of pediatric orthopedics. Part B.

[11]  X. Estivill,et al.  Molecular studies in 20 submicroscopic neurofibromatosis type 1 gene deletions , 1999, Human mutation.

[12]  A. Crawford,et al.  Neurofibromatosis in children: the role of the orthopaedist. , 1999, The Journal of the American Academy of Orthopaedic Surgeons.

[13]  R. Tenconi,et al.  Descriptive analysis of tibial pseudarthrosis in patients with neurofibromatosis 1. , 1999, American journal of medical genetics.

[14]  B. Reid,et al.  Loss of heterozygosity analysis using whole genome amplification, cell sorting, and fluorescence-based PCR. , 1999, Genome research.

[15]  D. Viskochil,et al.  Identification of NF1 mutations in both alleles of a dermal neurofibroma , 1996, Nature Genetics.

[16]  P. O'Connell,et al.  An Alu polymorphism intragenic to the neurofibromatosis type 1 gene (NF1) , 1991, Nucleic Acids Res..

[17]  H. Boyd.  Pathology and natural history of congenital pseudarthrosis of the tibia. , 1982, Clinical orthopaedics and related research.

[18]  V. M. Riccardi,et al.  Von Recklinghausen neurofibromatosis. , 1981, The New England journal of medicine.

[19]  McElhannon Fm.  Congenital pseudarthrosis of the tibia. , 1975 .

[20]  E. Yunis,et al.  Ultrastructure of congenital pseudarthrosis of the tibia. , 1973, Archives of pathology.

[21]  M. Bastos Ansart.  [Congenital pseudoarthrosis of the tibia]. , 1949, Clinica y laboratorio.