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NF1 mutations and clinical spectrum in patients with spinal neurofibromas
  1. L Kluwe1,
  2. M Tatagiba2,
  3. C Fünsterer3,
  4. V-F Mautner4
  1. 1Laboratory for Tumour Biology and Development Disorders, Department of Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, Germany
  2. 2Department of Neurosurgery, Medical College Hannover, Germany
  3. 3Hamburg-Othmarschen MRI Institute, Germany
  4. 4Department of Neurology, Klinikum Nord Ochsenzoll, Hamburg, Germany
  1. Correspondence to:
 Dr L Kluwe, Laboratory for Tumour Biology and Development Disorders, Department of Maxillofacial Surgery, University Hospital Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; 

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Neurofibromatosis 1 (NF1) is an autosomal dominant disorder associated with a variety of benign and malignant lesions such as café au lait spots, neurofibromas, phaeochromocytomas, pilocytic astrocytomas, and malignant peripheral nerve sheath tumours.1–3 With an incidence of 1 in 4000, NF1 is caused by genetic alterations of the NF1 gene located on 17q11.2.4–6 Consisting of 60 exons, the NF1 gene is a tumour suppressor gene which leads to tumorigenesis upon inactivation of both alleles.7–9

Spinal tumours cause neurological symptoms in about 2% of NF1 patients and can be detected in 40% of NF1 patients by magnetic resonance imaging (MRI).10 Patients with multiple spinal tumours but very few or no other clinical symptoms of NF1, including three multigenerational families,11–13 have been reported, suggesting a subgroup or a distinct genetic form of NF1, spinal neurofibromatosis (SNF).14 In one of these multigenerational families, a truncating mutation in exon 46 of the NF1 gene was found.13 However, no systematic study of the clinical spectrum of patients with spinal tumours and of the NF1 mutations associated with it has been carried out.

In this study, we performed a clinical and molecular examination of patients from 17 families with spinal tumours.


Neurofibromatosis type 1 (NF1) was diagnosed based on the NIH criteria.15 The protocol was approved by the institutional review board and all participants provided informed consent. The 17 index patients and 11 family members were examined in our NF clinic in Hamburg. Detailed MRI results of the full spine were available from the 17 patients and three affected family members.10

DNA was extracted from blood using a QIAamp Blood Kit from Qiagen (Hilden, Germany). Mutation analysis was performed by direct sequencing of all NF1 exons using a BigDye Sequencing kit as previously …

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