Neurofibromatosis 2 with peripheral neuropathies: Electrophysiological, pathological and genetic studies of a Taiwanese family
Article first published online: 26 JAN 2010
© 2010 Japanese Society of Neuropathology
Volume 30, Issue 5, pages 515–523, October 2010
How to Cite
Kuo, H.-C., Chen, S.-R., Jung, S.-M., Wu Chou, Y.-H., Huang, C.-C., Chuang, W.-L., Wei, K.-C. and Ro, L.-S. (2010), Neurofibromatosis 2 with peripheral neuropathies: Electrophysiological, pathological and genetic studies of a Taiwanese family. Neuropathology, 30: 515–523. doi: 10.1111/j.1440-1789.2009.01099.x
- Issue published online: 26 JAN 2010
- Article first published online: 26 JAN 2010
- Received 30 August 2009; revised 8 December 2009 and accepted 10 December 2009; published online 26 January 2010.
- electrophysiological study;
- neurofibromatosis type 2;
- peripheral neuropathy;
- sural nerve biopsy;
- “two-hit” hypothesis
The objective of this study was to assess peripheral nerve involvement and DNA mutation of the neurofibromatosis type 2 (NF2) gene (NF2) in a Taiwanese family with classic NF2. Eleven members (six symptomatic and five asymptomatic) of a family carrying NF2 underwent clinical examination, neuroimaging, and electrophysiological analysis. Mutation and linkage analyses were conducted on DNA samples prepared from peripheral blood (all individuals), a sural nerve biopsy specimen (one symptomatic member), and a tumor specimen (another symptomatic member). Six of the 11 members were diagnosed with classic NF2. DNA sequencing of the tumor specimen demonstrated a frameshift mutation with 756delC on exon 8 of NF2. Three affected subjects showed clinical variability of the neuropathic disorders. Electrophysiological studies demonstrated variation in the disease pattern and severity of peripheral nerve involvement in five affected subjects. The morphometric assessment of the sural nerve biopsy specimen showed a marked reduction in both large myelinated and unmyelinated fibre density and increased density of non-myelinating Schwann cell nuclei. Apart from numerous pathological nuclei of isolated Schwann cells, multiple profiles of non-myelinating Schwann cell subunits were apparent in the endoneurium. Schwann cell proliferation in association with first-hit mutation of the merlin gene might be responsible for the NF2-associated neuropathy. Sural nerve biopsy showed a progressive neuropathy in the disease. Further, we suggest nonmyelinating Schwann cells are involved in NF2 neuropathy.