Identification of NF2 germ-line mutations and comparison with neurofibromatosis 2 phenotypes |
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Authors: | L Kluwe Saskia Bayer M E Baser Wasim Hazim Wolfgang Haase Carsten Fünsterer V-F Mautner |
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Institution: | (1) Laboratory for Brain Tumor Biology, Department of Neurosurgery, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany, DE;(2) 11746 Bellagio Rd., #308, Los Angeles, CA 90049, USA, US;(3) Department of Ophthalmology, University Hospital Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany, DE;(4) Hamburg-Othmarschen MRI Institute, Othmarscher Kirchenweg 166, D-22763 Hamburg, Germany, DE;(5) Neurology Department, Allgemeines Krankenhaus Ochsenzoll, Langenhorner Chaussee 560, D-22419 Hamburg, Germany Tel.: +49 40-5271 2872; Fax: +49 40-5277 462, DE |
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Abstract: | Neurofibromatosis 2 (NF2) is an autosomal inherited disorder that predisposes carriers to nervous system tumors. To examine
genotype-phenotype correlations in NF2, we performed mutation analyses and gadolinium-enhanced magnetic resonance imaging
of the head and full spine in 59 unrelated NF2 patients. In patients with vestibular schwannomas (VSs) or identified NF2 mutations, the mild phenotype was defined as <2 other intracranial tumors and ≤ 4 spinal tumors, and the severe phenotype
as either ≥ 2 other intracranial tumors or > 4 spinal tumors. Nineteen mutations were found in 20 (34%) of the patients and
were distributed in 12 of the 17 exons of the NF2 gene, including intron-exon boundaries. Seven mutations were frameshift, six were nonsense, four were splice site, two were
missense, and one was a 3-bp in frame deletion. The nonsense mutations included one codon 57 and two codon 262 C→T transitions
in CpG dinucleotides. The frameshift and nonsense NF2 mutations occurred primarily in patients with severe phenotypes. The two missense mutations occurred in patients with mild
phenotypes, and three of the four splice site mutations occurred in families with both mild and severe phenotypes. Truncating
NF2 mutations are usually associated with severe phenotypes, but the association of some mutations with mild and severe phenotypes
indicates that NF2 expression is influenced by stochastic, epigenetic, or environmental factors.
Received: 4 July 1996 |
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