Y F Liu

Publications (2)11.79 Total impact

• Article: Population-specific spectrum of NOTCH3 mutations, MRI features and founder effect of CADASIL in Chinese.

  Yi-Chung Lee, Chin-San Liu, Ming-Hong Chang, Kon-Ping Lin, Jong-Ling Fuh, Yi-Chu Lu, Ya-Fen Liu, Bing-Wen Soong
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  ABSTRACT: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary disorder caused by NOTCH3 mutations and characterized by recurrent subcortical infarctions, dementia and leukoencephalopathy. So far, most clinical, molecular and neuroimaging information has come from Caucasians. Therefore, we investigated the spectrum of NOTCH3 mutations and MRI features in CADASIL patients of Chinese origin on Taiwan. Mutational analysis of NOTCH3 exons 2 to 23 by direct nucleotide sequencing was performed in patients with clinically suspected CADASIL. MRI findings were retrospectively evaluated and scored using a modified Schelten's scale. Nine different point mutations of NOTCH3 were identified in 21 unrelated patients. Intriguingly, 47.6 % were in exon 11, and 19 % in each of exon 4 and 18. R544C was very common and present in all patients with a mutation in exon 11. Many patients with NOTCH3 R544C share the same haplotype linked to the mutation using markers D19S929 and D19S411, which flank the NOTCH3. The sensitivity of T2-weighted MRI detecting anterior temporal abnormality was only 42.9 %. Furthermore, the neuroimaging evidence of intracerebral hemorrhage (ICH) was present in 23.8 % of the 21 patients. A population-specific mutational spectrum of CADASIL was found in the Chinese patients on Taiwan. The Chinese patients carrying NOTCH3 R544C may descend from a common ancestor. Anterior temporal hyperintensity on T2-weighted MRI may not be a sensitive marker for CADASIL. ICH is a relatively common manifestation of CADASIL in East Asians, especially in the presence of hypertension.
  Journal of Neurology 03/2009; 256(2):249-55. · 3.47 Impact Factor
• Article: MPZ mutation G123S characterization: evidence for a complex pathogenesis in CMT disease.

  Y C Lee, C T R Yu, K P Lin, M H Chang, S L Hsu, Y F Liu, Y C Lu, B W Soong
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  ABSTRACT: To characterize the clinical and cellular phenotypes of a novel MPZ mutation identified in a Chinese family with Charcot-Marie-Tooth (CMT) disease type 1B. The family was evaluated clinically, electrophysiologically, pathologically, and genetically. The wild-type and mutant P(0) fused with fluorescent proteins were expressed in vitro to monitor their intracellular trafficking. Adhesion assay was also performed to evaluate the adhesiveness of cells. The novel MPZ mutation, c.367G>A, is associated with a late-onset demyelinating CMT phenotype with autosomal dominant inheritance. The median motor nerve conduction velocities of patients in this family ranged from 15.7 to 19.6 m/second. The neuropathologic studies from a sural nerve biopsy revealed a severe loss of myelinated fibers, and some onion bulb formation with clusters of regenerative fibers. Fluorescence analysis demonstrated that the mutant protein was retained ectopically in the endoplasmic reticulum and Golgi apparatus. Adhesion assay demonstrated a defective adhesiveness of cells expressing the mutant P(0)G123S protein. The novel P(0)G123S mutation is associated with typical findings of late-onset demyelinating polyneuropathy in the electrophysiologic and pathologic studies, putatively resulting from aberrant intracellular trafficking of the mutant P(0) protein, which compromises the adhesiveness of the cells.
  Neurology 02/2008; 70(4):273-7. · 8.31 Impact Factor