Neurofibromatosis 2 with peripheral neuropathies: Electrophysiological, pathological and genetic studies of a Taiwanese family.
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.
Kuo
Hung-Chou
HC
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.
Chen
Shyue-Ru
SR
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.
Jung
Shih-Ming
SM
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.
Wu Chou
Yah-Huei
YH
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.
Huang
Chin-Chang
CC
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.
Chuang
Wen-Li
WL
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.
Wei
Kuo-Chen
KC
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.
Ro
Long-Sun
LS
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.
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