title: Is double inactivation of the Nf1 gene responsible for the development of congenital pseudarthrosis of the tibia associated with NF1?
abstract: The pathogenic mechanism responsible for congenital pseudarthrosis of the tibia (CPT) is not well understood although the possibility of double inactivation of the neurofibromatosis type 1 (Nf1) gene has been suggested. In the present study, loss of heterozygosity was investigated in fibrous hamartoma tissues harvested from 16 patients with CPT associated with NF1 using four genetic markers that span the Nf1 gene. Based on the assumption that a single cell with double inactivation of Nf1 would undergo clonal growth and cause fibrous hamartoma, we investigated clonality in fibrous hamartoma tissues by analyzing X-chromosome inactivation patterns in 11 female patients. Loss of Nf1 heterozygosity in fibrous hamartoma tissues was observed at one or two genetic markers in 4 out of the 16 patients tested. In clonality assays, 3 of 11 patients showed a clonal growth pattern, 5 a non-clonal pattern, and 3 were non-informative. These findings support that double inactivation of the Nf1 gene and subsequent clonal growth could be a pathogenic feature of the fibrous hamartoma tissue at least in some of the CPT but might not be essential requirements of CPT development.
authors.affiliation: Department of Orthopaedic Surgery, Eulji University College of Medicine, 1306 Dunsan-dong, Seo-gu, Daejeon, 302-799, South Korea.
authors.forename: Sang Min
authors.initials: SM
authors.lastname: Lee
authors.forename: In Ho
authors.initials: IH
authors.lastname: Choi
authors.forename: Dong Yeon
authors.initials: DY
authors.lastname: Lee
authors.forename: Hye Ran
authors.initials: HR
authors.lastname: Lee
authors.forename: Moon Seok
authors.initials: MS
authors.lastname: Park
authors.forename: Won Joon
authors.initials: WJ
authors.lastname: Yoo
authors.forename: Chin Youb
authors.initials: CY
authors.lastname: Chung
authors.forename: Tae-Joon
authors.initials: TJ
authors.lastname: Cho
mesh_terms: D002648:Child; D002675:Child, Preschool; D005260:Female; D016514:Genes, Neurofibromatosis 1; D006222:Hamartoma / Q000209:etiology* / Q000473:pathology; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D008297:Male; D011542:Pseudarthrosis / Q000151:congenital* / Q000235:genetics / Q000473:pathology; D013977:Tibia / Q000473:pathology*