MUTATION IN BRIEF HUMAN MUTATION Mutation in Brief #489 (2002) Online © 2002 WILEY-LISS, INC. DOI: 10.1002/humu.9018 Received 28 November 2001; accepted 21 December 2001. NF1 Mutations in Neurofibromatosis 1 Patients with Plexiform Neurofibromas Lan Kluwe 1 , Reinhard E. Friedrich 2 , Bruce Korf 3 , Raimund Fahsold 4 , and Victor-F. Mautner 5 1 Laboratory for Brain Tumor Biology, Department of Neurosurgery and 2 Department of Maxillofacial Surgery, University Hospital Hamburg-Eppendorf, Germany; 3 Partner Center for Human Genetics, Harvard Institutes of Medicine, Boston, USA; 4 Gemeinschaftspraxis B. Prager & A. Junge, Dresden; 5 Department of Neurology, Klinikum Nord Ochsenzoll, Hamburg, Germany. *Correspondence to: Dr. Lan Kluwe, Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Martinistr. 52, 20246 Hamburg, Germany; Tel.: 49-40-42803-2767; Fax: 49-40- 79410217; E-mail: kluwe@uke.uni-hamburg.de Contract grant sponsors: Deutsche Krebshilfe; US Army; Hamburger Stiftung zur Förderung der Krebskämpfung; Contract grant numbers: 70-2794-De 1; ADMD17-98-1-8611; 141, 151. Communicated by Mark H. Paalman Neurofibromatosis 1 (NF1) is an autosomal dominant disorder caused by genetic alterations of the NF1 gene on 17q11.2. About 30% of NF1 patients develop plexiform neurofibromas (PNFs), which often cause severe clinical deficits. To determine whether there is a certain genotype underlying PNFs or subtypes of PNFs, we screened 42 NF1 patients from 41 families with PNFs for mutations in the NF1 gene. In 33 out of the 41 (80%) unrelated patients NF1 mutations were found, 24 are novel while the other 9 have been described in previous studies. The 33 mutations included 23 nonsense and frameshift, six splice and four missense mutations. The tumors in these patients had various sizes and features/growth characteristics. No correlation was found between the type or location of the NF1 mutations and size, location or feature of the PNFs, suggesting that many types of NF1 mutations can lead to development of PNFs. © 2002 Wiley-Liss, Inc. KEY WORDS: Neurofibromatosis 1; NF1; Plexiform neurofibroma; PNF; tumor INTRODUCTION Neurofibromatosis 1 (NF1; MIM# 162200) is an autosomal dominant disorder associated with a variety of benign and malignant lesions such as café-au-lait spots, neurofibromas, malignant peripheral nerve sheath tumors, pheochromocytomas and pilocytic astrocytomas (Huson, 1989; Huson et al., 1994; Marchuk et al., 1994). About 30% of NF1 patients (Huson et al., 1988) also develop plexiform neurofibromas (PNFs), which originate from subcutaneous or visceral peripheral nerves and involve multiple fascicles extending along the length of a nerve. PNFs vary in size and can be extremely large. They can be roughly divided into three types based on growth patterns: flat, displacing and invasive. Flat PNFs are isolated tumors that do not cross tissue planes and are amenable to complete or nearly complete surgical resection. Some of the displacing PNFs can also be surgically removed if they are not large and do not infiltrate the nerves. Invasive PNFs extend through multiple tissue planes