title: A patient severely affected by spinal neurofibromas carries a recurrent splice site mutation in the NF1 gene.
abstract: Spinal neurofibromas are found in up to 38% of NF1 patients. However, they cause clinical implications only in about 5% of the patients. In contrast, multiple symptomatic spinal neurofibromas are the main clinical finding in patients with familial spinal neurofibromatosis. Familial spinal neurofibromatosis has been considered to be a distinct clinical form of neurofibromatosis. Linkage analysis in two families and identification of a NF1 gene mutation in a third family strongly associate spinal neurofibromatosis with the NF1 gene. We describe a NF1 patient who satisfies the NIH diagnostic criteria and has severe spinal involvement with bilateral spinal root neurofibromas at every level. A recurrent splice site mutation (IVS19b-3C>G) was identified in the NF1 gene in the patient. We discuss the possibility that the clinical picture of this patient represents an additional example of spinal neurofibromatosis. By comparison of the clinical expression of NF1 in this patient and that in another patient with the identical mutation the hypothesis that spinal neurofibromatosis is associated with a particular mutation is highly unlikely. The involvement of other genes linked to the NF1 gene or modifying genes is currently the most likely explanation for the clinical phenotype of spinal neurofibromatosis.
authors.affiliation: Institut für Medizinische Biologie, University of Vienna, Austria. katharina.wimmer@univie.ac.at
authors.forename: Katharina
authors.initials: K
authors.lastname: Wimmer
authors.forename: Manfred
authors.initials: M
authors.lastname: Mühlbauer
authors.forename: Markus
authors.initials: M
authors.lastname: Eckart
authors.forename: Tom
authors.initials: T
authors.lastname: Callens
authors.forename: Helga
authors.initials: H
authors.lastname: Rehder
authors.forename: Thomas
authors.initials: T
authors.lastname: Birkner
authors.forename: Jules G
authors.initials: JG
authors.lastname: Leroy
authors.forename: Christa
authors.initials: C
authors.lastname: Fonatsch
authors.forename: Ludwine
authors.initials: L
authors.lastname: Messiaen
mesh_terms: D000328:Adult; D005260:Female; D006801:Humans; D009154:Mutation; D009456:Neurofibromatosis 1 / Q000235:genetics*; D022821:RNA Splice Sites; D013120:Spinal Cord Neoplasms / Q000235:genetics*; D013126:Spinal Nerve Roots
chemical_list: D022821:RNA Splice Sites