Neurofibromatosis 2 with peripheral neuropathies: Electrophysiological, pathological and genetic studies of a Taiwanese family

• Published in: Neuropathology Vol. 30; no. 5; pp. 515 - 523
• Main Authors: Kuo, Hung-Chou, Chen, Shyue-Ru, Jung, Shih-Ming, Wu Chou, Yah-Huei, Huang, Chin-Chang, Chuang, Wen-Li, Wei, Kuo-Chen, Ro, Long-Sun
• Format: Journal Article
• Language: English
• Published: Melbourne, Australia Blackwell Publishing Asia 01.10.2010
• Subjects: "two-hit" hypothesis; Adult; Asian Continental Ancestry Group; Biopsy; DNA sequencing; Electrophysiological recording; electrophysiological study; Exons; Frameshift Mutation; Genes, Neurofibromatosis 2; Humans; Image processing; Linkage analysis; Male; Middle Aged; Neural Conduction; Neurofibromatosis 2; Neurofibromatosis 2 - complications; Neurofibromatosis 2 - genetics; Neurofibromatosis 2 - pathology; Neurofibromatosis 2 - physiopathology; neurofibromatosis type 2; Neurofibromin 2; Neuroimaging; Pedigree; Peripheral blood; Peripheral nerves; Peripheral Nervous System Diseases - complications; Peripheral neuropathy; Schwann cells; Schwann Cells - pathology; Schwann Cells - ultrastructure; sural nerve; Sural Nerve - physiopathology; Sural Nerve - ultrastructure; sural nerve biopsy; Taiwan; Tumors; Young Adult; Taiwan; sural nerve biopsy; neurofibromatosis type 2; electrophysiological study; peripheral neuropathy; “two-hit” hypothesis
• ISSN: 0919-6544; 1440-1789; 1440-1789
• DOI: 10.1111/j.1440-1789.2009.01099.x

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.