HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Correspondence: Submit a response Alert me when this article is cited Alert me when Correspondence are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by MacCollin, M. Articles by Louis, D. N. Search for Related Content PubMed PubMed Citation Articles by MacCollin, M. Articles by Louis, D. N.

Familial schwannomatosis

Exclusion of the NF2 locus as the germline event

From the Departments of Neurology (Dr. MacCollin, C. Willett, and B. Heinrich), Neurosurgery (Dr. Jacoby), and Pathology (Dr. Louis), Massachusetts General Hospital, Charlestown; The Harvard Institute of Human Genetics (J.S. Acierno Jr.), Harvard Medical School, Boston, MA; and the Division of Neuropathology (Dr. Perry), Washington University School of Medicine, St. Louis, MO.

Address correspondence and reprint requests to Dr. Mia MacCollin, Neuroscience Center, MGH East, Bldg. 149, 13th St., Charlestown, MA 02129; e-mail: maccollin{at}helix.mgh.harvard.edu

Background: Schwannomatosis is a recently recognized disorder, defined as multiple pathologically proven schwannomas without vestibular tumors diagnostic of neurofibromatosis 2 (NF2). Some investigators have questioned whether schwannomatosis is merely an attenuated form of NF2.

Methods: The authors identified eight families in which a proband met their diagnostic criteria for schwannomatosis. Archived and prospectively acquired tumor specimens were studied by mutational analysis at the NF2 locus, loss of heterozygosity analysis along chromosome 22, and fluorescent in situ hybridization analysis of NF2 and the more centromeric probe BCR. Linkage analysis could be performed in six of eight families.

Results: Clinical characterization of these kindreds showed that no affected family member harbored a vestibular tumor. Molecular analysis of 28 tumor specimens from 17 affected individuals in these kindreds revealed a pattern of somatic NF2 inactivation incompatible with our current understanding of NF2 as an inherited tumor suppressor gene syndrome. Linkage analysis excluded the NF2 locus in two kindreds, and showed a maximum lod score of 6.60 near the more centromeric marker D22S1174.

Conclusions: Schwannomatosis shows clinical and molecular differences from NF2 and should be considered a third major form of neurofibromatosis. Further work is needed to identify the inherited genetic element responsible for familial schwannomatosis.

This article has been cited by other articles:

				J. Xian, X. Xu, Z. Wang, B. Yang, B. Li, F. Man, Q. Chen, J. Shi, and Y. Zhang MR Imaging Findings of the Uveal Schwannoma AJNR Am. J. Neuroradiol., April 1, 2009; 30(4): 769 - 773. [Abstract] [Full Text] [PDF]

				J J Swensen, J Keyser, C M Coffin, J A Biegel, D H Viskochil, and M S Williams Familial occurrence of schwannomas and malignant rhabdoid tumour associated with a duplication in SMARCB1 J. Med. Genet., January 1, 2009; 46(1): 68 - 72. [Abstract] [Full Text] [PDF]

				M. MacCollin, E. A. Chiocca, D. G. Evans, J. M. Friedman, R. Horvitz, D. Jaramillo, M. Lev, V. F. Mautner, M. Niimura, S. R. Plotkin, et al. Diagnostic criteria for schwannomatosis Neurology, June 14, 2005; 64(11): 1838 - 1845. [Abstract] [Full Text] [PDF]

				M Ruggieri, P Pavone, A Polizzi, M D. Pietro, A Scuderi, A Gabriele, A Spalice, and P Iannetti Ophthalmological manifestations in segmental neurofibromatosis type 1 Br J Ophthalmol, November 1, 2004; 88(11): 1429 - 1433. [Abstract] [Full Text] [PDF]