Showing papers by "Bing-Wen Soong published in 2010"

Transmissible spongiform encephalopathies with P102L mutation of PRNP manifesting different phenotypes: clinical, neuroimaging, and electrophysiological studies in Chinese kindred in Taiwan.

Abstract: A P102L point mutation in the prion protein gene (PRNP) usually causes Gerstmann–Straussler–Scheinker disease (GSS), which is a rare hereditary transmissible spongiform encephalopathy (TSE). The clinical features include ataxia in 50s age group with subsequent dementia, spastic paraparesis and extrapyramidal signs. Many families have been reported from the Caucasian population, but only one from the Chinese. We hereby report a large Chinese family with P102L mutation of PRNP whose clinical manifestations at onset were intriguingly heterogeneous, either rapidly progressive dementia with scanty other neurological features or slowly progressive ataxia followed by cognitive impairment. The four-generation pedigree included eight patients with a mean age at onset of 36.9 ± 12.9 (mean ± SD) years. Mean disease duration to death in the four patients was 5.5 ± 1.7 (mean ± SD) years. Molecular analysis revealed a P102L mutation and M129 polymorphism in the PRNP gene in all affected individuals. TSE with P102L mutation of PRNP appears to have a remarkably variable phenotypic expressivity that may change with time and does not appear related to the codon 129 polymorphism.

Cellular characterization of MPZ mutations presenting with diverse clinical phenotypes

Abstract: Mutations in MPZ, which encodes myelin protein zero (P0), may lead to different subtypes of Charcot-Marie-Tooth disease (CMT). The aim of this study was to characterize the cellular manifestations of various MPZ mutations associated with CMT1, Dejerine-Sottas syndrome (DSS) and CMT2, and to correlate their cellular and clinical phenotypes. Nine P0 mutants associated with CMT1 (P0S63F, R98H, R277S, and S233fs), DSS (P0 I30T and R98C), and CMT2 (P0S44F, D75V, and T124M), were investigated. Wild-type and mutant P0 fused with fluorescent proteins were expressed in vitro to monitor their intracellular localization. An adhesiveness assay was used to evaluate the adhesiveness of the transfected cells. Protein localization and cell adhesiveness of each mutant protein were compared and correlated with their clinical phenotypes. Three different intracellular localization patterns of the mutant P0 were observed. Wild-type P0, P0I30T, S44F, S63F, D75V, T124M, and R227S were mostly localized on the cell membrane, P0R98H, and R98C were found in the endoplasmic reticulum (ER) or Golgi apparatus, and P0S233fs formed aggregates within the ER. Cells expressing mutant P0, as compared with those expressing wild-type P0, demonstrated variable degrees of reduction in the cell adhesiveness. The molecular patho-mechanisms of MPZ mutations are likely very complex and the clinical phenotype must be influenced by many genetic or environmental factors. This complexity may contribute to the highly variable clinical manifestations resulting from different MPZ mutations.

Gluten sensitivity: associated sporadic cerebellar ataxia in Taiwan.

Abstract: Purpose: Gluten sensitivity (GS) is related to the pathogenesis of sporadic or hereditary ataxia. Methods: Total of 194 healthy controls and patients with either hereditary ataxia (n=207) or sporadic ataxia (n=361) were tested for the circulating gluten-related autoantibodies which serve as biomarkers to interpret the existence of GS. Results: The incidences of GS in each population were 1% in normal subjects, 2% in hereditary ataxia patients and 9% in sporadic ataxia patients. High serum level of anti-gliadin IgG/IgA and t-transglutaminase IgA were disclosed at the sporadic ataxia patients compared with normal subjects. However, the anti-gliadin IgG is more specific to the disease of sporadic ataxia. Conclusion: Relatively higher incidence of GS was found in the population of sporadic ataxia patients but not in either normal subjects or hereditary ataxia patients in Taiwan. Anti-gliadin IgG still is a very powerful indicator to implicate the immune-related sporadic ataxia and we conclude that GS-related sporadic ataxia exists in Taiwan with linkage to autoimmune events.