Publications (4)3.91 Total impact
- [Show abstract] [Hide abstract] 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.
- [Show abstract] [Hide abstract] ABSTRACT: The precise definition of the International Association for the Study of Pain (IASP) revised in 2008 states that neuropathic pain is a type of pain arising as a direct consequence of a lesion or disease affecting the somatosensory system. This kind of pain is due to long-term dysfunction of the nervous system and is clinically characterized by spontaneous and evoked types of chronic pain, which are involved by various distinct pathophysiological mechanisms in the peripheral and central nervous systems. It is relatively common, with an incidence estimated at 0.6% to 1.5% in the US population. Unfortunately, there was no effective therapy until recently. Our research team found an effective strategy in treating neuropathic pain that resulted from interactions between leukocyte-derived opioid peptides and their receptors on peripheral sensory neurons. Here, we briefly review granulocyte colony stimulating factor (G-CSF) therapy in an animal model of neuropathic pain. Our studies also proved that G-CSF can increase the number of opioid-contained polymorphonuclear cells and significantly relieve neuropathic pain. These studies have led to an increased understanding of the opioids and cytokines -modulating peripheral analgesia effect on neuropathic pain, which opens a new avenue in its treatment.
- [Show abstract] [Hide abstract] ABSTRACT: Current molecular diagnostic methods in detecting Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsy (HNPP) diseases are either not sensitive or time-consuming and costing. The aims of this study are improving the accuracy and speeding up the diagnosis. We developed real-time quantitative PCR (QPCR) and three polymorphic short tandem repeats (STRs) methods to test 53 unrelated CMT1A patients, 12 unrelated HNPP patients and 100 normal control subjects. QPCR in detection of pmp22 gene duplication (CMT1A) and deletion (HNPP) showed a sensitivity of 100.00% (53/53) and 100.00% (12/12), respectively. And this method also showed a specificity of 100% (100/100) in CMT1A and 100% (100/100) in HNPP, respectively. In contrast, using three polymorphic STRs method showed a sensitivity of 50/53 (94%) in CMT1A and 12/12 (100.00%) of HNPP patients, respectively. And this method showed a specificity of 97% (100/103) in CMT1A and 100% (100/100) in HNPP, respectively. QPCR and three STRs methods both demonstrate a rapid and robust diagnosis with almost complete informativeness. The high sensitivity and heterozygosity of these three polymorphic markers in detecting CMT1A/HNPP subjects of Caucasian and Chinese showed the potential to become pan-ethnic screening markers in the future.
- [Show abstract] [Hide abstract] ABSTRACT: Studies of distal myopathy with rimmed vacuoles (DMRV) revealed that most patients had mutations in the UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) gene. However, the correlation between GNE mutations and clinical features was not fully understood. To report the correlation between the clinical features and genetic analysis of DMRV patients. The clinical presentations, histopathological findings, image studies, and genetic analyses of two patients with DMRV from a Taiwanese family were studied. Two compound heterozygous mutations, Ile 241 Ser and Arg 246 Gln, located in the epimerase domain, were identified in both patients, who were of the same generation. In addition, the elder sister showed a progressive muscular dystrophy course with severe quadriceps and trunk muscle involvement. The compound heterozygous mutations in the epimerase domain of the GNE gene are important in the severe phenotype of DMRV. However, the mechanisms leading to this phenotypic heterogeneity still remain to be elucidated.
Chang Gung Memorial Hospital
T’ai-pei, Taipei, Taiwan
- Division of Neurology