Genotype-Phenotype Correlates in Taiwanese Patients with Early-Onset Recessive Parkinsonism

We screened for mutations in the PARKIN, DJ-1, and PINK1 genes in a Taiwanese cohort (68 probands; 58 sporadic and 10 familial) with early- onset parkinsonism (EOP, onset <50 years of age). We identified 9 patients harboring mutations in PARKIN (three compound heterozygous and six single heterozygous carriers), 3 patients with heterozygous PINK1 mutations ( including two novel substitutions M341I and P209A ), and no DJ-1 mutations . Our frequencies of PARKIN (two allele mutation, 4.4%; single allele, 8.8 %) and PINK1 ( single heterozygous, 4.4%) mutations in Taiwanese-Chinese are similar to those in Caucasian and other Asian EOP patients. Although the role of heterozygosity of recessive genes in EOP remains to be resolved, molecular analysis and functional imaging will play a decisive role in differential diagnosis and determined therapeutic strategy

The systems biology of neurofibromatosis type 1 - Critical roles for microRNA

Neurofibromatosis type 1 (NF1) is one of the most common inherited neurological disorders with a wide range of clinical manifestations. The causative gene for NF1 encodes a multi-domain protein, neurofibromin, which interacts with RAS through its RAS-GAP domain. Dysfunction of neurofibromin results in abnormal RAS activation in the cells which has been thought to be the main process in the initiation and progression of NF1. Based on this hypothesis, inhibitors for various RAS mediated signaling pathways are in different stages of clinical trials to treat NF1 or NF1-associated symptoms. While the molecular genetics of NF1 has made significant progress in recent years, the underlying etiology and progression of NF1 are yet to be fully understood. Besides review and summarization of the latest results of genetic, transcriptomic and microRNA studies associated with NF1, we conducted limited post-hoc analysis to illustrate the importance of using integrated systems biology approach to study complex diseases like NF1. (c) 2011 Elsevier Inc. All rights reserved

Rs5848 Variant of Progranulin Gene Is a Risk of Alzheimers Disease in the Taiwanese Population

Progranulin is the precursor of granulins, and its downregulation may lead to neurodegeneration. The single- nucleotide polymorphism rs5848 increases the risk of Alzheimers disease AD. We explored the association between alleles of rs5848 and the risk of AD in the Taiwanese population. The frequency of the homozygous TT genotype 16.4 vs. 10.0% increased in AD subjects by an odds ratio OR of 1 .87 p = 0.03 corrected for APOE epsilon 4, age and gender. Interaction between age and homozygous TT genotype accentuated the risk of AD OR 4.44, p < 0.001. The homozygous TT genotype of rs5848 may play a role in the genetic risk of AD development, especially in the elderly