title: Neurofibromatosis 2 with peripheral neuropathies: Electrophysiological, pathological and genetic studies of a Taiwanese family.
abstract: 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.
authors.affiliation: Departments of Neurology,Pathology,Human Genetics Laboratory, Department of Medical Research andNeurosurgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Hung-Chou
authors.initials: HC
authors.lastname: Kuo
authors.affiliation: Departments of Neurology,Pathology,Human Genetics Laboratory, Department of Medical Research andNeurosurgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Shyue-Ru
authors.initials: SR
authors.lastname: Chen
authors.affiliation: Departments of Neurology,Pathology,Human Genetics Laboratory, Department of Medical Research andNeurosurgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Shih-Ming
authors.initials: SM
authors.lastname: Jung
authors.affiliation: Departments of Neurology,Pathology,Human Genetics Laboratory, Department of Medical Research andNeurosurgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Yah-Huei
authors.initials: YH
authors.lastname: Wu Chou
authors.affiliation: Departments of Neurology,Pathology,Human Genetics Laboratory, Department of Medical Research andNeurosurgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Chin-Chang
authors.initials: CC
authors.lastname: Huang
authors.affiliation: Departments of Neurology,Pathology,Human Genetics Laboratory, Department of Medical Research andNeurosurgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Wen-Li
authors.initials: WL
authors.lastname: Chuang
authors.affiliation: Departments of Neurology,Pathology,Human Genetics Laboratory, Department of Medical Research andNeurosurgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Kuo-Chen
authors.initials: KC
authors.lastname: Wei
authors.affiliation: Departments of Neurology,Pathology,Human Genetics Laboratory, Department of Medical Research andNeurosurgery, Chang Gung Memorial Hospital at Linkou and College of Medicine, Chang Gung University, Taipei, Taiwan.
authors.forename: Long-Sun
authors.initials: LS
authors.lastname: Ro
mesh_terms: D000328:Adult; D044466:Asian People; D016368:Frameshift Mutation; D016515:Genes, Neurofibromatosis 2; D006801:Humans; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction; D016518:Neurofibromatosis 2 / Q000150:complications / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology*; D010375:Pedigree; D010523:Peripheral Nervous System Diseases / Q000150:complications*; D012583:Schwann Cells / Q000473:pathology / Q000648:ultrastructure; D013497:Sural Nerve / Q000503:physiopathology / Q000648:ultrastructure; D013624:Taiwan; D055815:Young Adult