Neurofibromatosis type 1 (NF1), also known as von Recklinghausen disease, is a common autosomal dominant genetic disorder affecting approximately 1 in 3000 individuals worldwide. NF1 results from heritable or spontaneous mutations of the NF1 tumor suppressor gene, encoding the protein neurofibromin, which functions to negatively regulate Ras-activity. Although neurofibromas are considered the hallmark feature of NF1, up to 70 percent of NF1 patients develop both generalized and focal osseous defects including short stature, kyphoscoliosis, osteopenia/osteoporosis, fractures, and pseudarthrosis (fracture non-union). While defective osteoblast bone anabolism has been implicated as a central factor in the pathogenesis of NF1 associated skeletal deficits, recent data suggests that NF1 (Nf1) haploinsufficiency within the hematopoietic compartment, particularly in osteoclasts and myeloid progenitors, plays a pivotal role in engendering NF1 osseous manifestations. In this chapter, we review the latest data from clinical studies and murine models demonstrating a requirement for hematopoietic derived NF1 (Nf1) haploinsufficient osteoclasts and their progenitors in the pathogenesis of multiple NF1 skeletal deficits.
|Original language||English (US)|
|Title of host publication||Neurofibromatosis: Diagnosis, Management and Clinical Outcomes|
|Publisher||Future Medicine Ltd.|
|Number of pages||30|
|ISBN (Print)||9781634632485, 9781634632294|
|State||Published - Oct 1 2014|
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