title: Aetiology of spinal deformities in neurofibromatosis 1: new hypotheses.
abstract: Neurofibromatosis 1 is a common heritable disorder. The gene causing neurofibromatosis 1 had been recognized and the protein encoded by this gene, neurofibromin, was supposed to play a role in development of various tissues. Neurofibromin was found to have GTP-ase (GAP) domain against small p21 ras. IQGAP1 is another human ras-specific GAP that was found to have calmodulin-binding motifs. Spinal deformities in cases of neurofibromatosis 1 are generally classified into dystrophic and non-dystrophic. Aetiologies of both types are still unknown. We hypothesize that muscle pathology could be the initiating factor for non-dystrophic curves due to neurofibromin deficiency and/or increase of the level of IQGAP. Dystrophic curves might begin as a developmental error due to neurofibromin deficiency in bone. Melatonin deficiency, increased serotonin level with disturbed melatonin-serotonin interactions and calmodulin antagonism by increased IQGAP1 may be responsible for progression of both types of spinal deformities in neurofibromatosis 1.
authors.affiliation: Orthopaedic Department, Faculty of Medicine, Kanazawa University, Kanazawa, Ishikawa, Japan.
authors.forename: M E
authors.initials: ME
authors.lastname: Abdel-Wanis
authors.forename: N
authors.initials: N
authors.lastname: Kawahara
mesh_terms: D002147:Calmodulin / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008550:Melatonin / Q000172:deficiency / Q000502:physiology; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D009456:Neurofibromatosis 1 / Q000235:genetics / Q000503:physiopathology*; D025542:Neurofibromin 1; D013131:Spine / Q000002:abnormalities*; D020703:ras GTPase-Activating Proteins / Q000378:metabolism
chemical_list: D002147:Calmodulin; D002352:Carrier Proteins; C101203:IQ motif containing GTPase activating protein 1; D009419:Nerve Tissue Proteins; D025542:Neurofibromin 1; D020703:ras GTPase-Activating Proteins; D008550:Melatonin