Abstract Details

Title The Mutational Spectrum in a Cohort with Familial and Sporadic Amyotrophic Lateral Sclerosis among the Han Chinese in Taiwan

Topic Anterior Horn

Presentation(s) P05 - (-)

Poster/Presentation
Number 082

Objective

Background BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by relentlessly progressive loss of motor neurons. Mutations in at least 15 genes have been described to cause familial ALS (FALS), which may account for 10-20% of ALS cases.

Design/Methods DESIGN/METHODS: Mutational analyses of the SOD1, TARDBP, FUS, OPTN, VCP, UBQLN2, and PFN1 genes were carried out by direct sequencing in 139 unrelated patients with ALS, including 28 with FALS and 111 with sporadic ALS (SALS). The CAG repeat sizes in ATXN2 and the GGGGCC hexanucleotide repeat expansion in C9ORF72 of the patients were also investigated.

Results RESULTS: Mutations have been identified in 30 of the 139 patients (21.6%), including 19 with FALS (67.9%; 19/28) and 11 with SALS (9.9%; 11/111). Among the 28 FALS patients, 7 were found to have SOD1 mutations (p.T137R in 2, and p.L8V, p.G10A, p.G85R, p.L106F and p.G138E in 1), 5 had TARDBP mutations (p.M337V in 4 and p.N378D in1), 5 had the C9ORF72 repeat expansion, and 2 had FUS mutations (p.H517D and p.R521H). Among the 111 SALS cases, 3 were found to have SOD1 mutations (p.G16S, p.G37R, and p.C111Y), 3 had intermediate-length CAG expansions (28, 32, and 33 CAG repeats), 2 had the C9ORF72 repeat expansion, 1 had a TARDBP mutation (p.S375G), 1 had a FUS mutation (p.R521H), and 1 had an OPTN mutation (p.L494W). No patient was found to have VCP, UBQLN2, or PFN1 mutation.

Conclusions CONCLUSIONS: This study clearly demonstrates the distribution and frequency of mutations in a Taiwanese ALS cohort of Chinese origin, and supports the global importance of mutations in the SOD1, TARDBP, C9ORF72, ATXN2 and FUS genes in ALS.

Authors/Disclosures
Yi-Chung Lee, MD, FAAN (Taipei Veterans General Hospital) PRESENTER	The institution of Dr. Lee has received research support from National Science and technology Council Taiwan . The institution of Dr. Lee has received research support from Taipei Veterans General Hospital Taiwan.
Bing-Wen Soong, MD, PhD, FAAN	No disclosure on file
Ching Piao Tsai, MD (Taipei Vaterans General Hospital)	No disclosure on file
Tania Kuempfel, MD (Institut for Klinische Neuroimmunologie)	Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Alexion. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for UCB Pharma. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Alexion. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Dr. Kuempfel has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Amgen/Horizon.

��ɫ��

��ɫ��