Abstract Details

Title Contribution of Major Amyotrophic Lateral Sclerosis Related Genes to the Etiology of the Disease in Chinese

Topic Aging and Dementia

Presentation(s) P05 - (-)

Poster/Presentation
Number 098

Objective

Background BACKGROUND: Mutations in SOD1, ANG, TARDBP, FUS, VCP, C9ORF72, and PFN1 genes have been identified in ALS patients.

Design/Methods DESIGN/METHODS: Screening for mutations of SOD1, ANG, TARDBP, FUS, VCP, C9ORF72, and PFN1 genes was consecutively carried out in 20 index FALS patients, 324 SALS patients, and 245 healthy controls admitted to Peking Union Medical College Hospital.

Results RESULTS: Overall, mutations were detected in 30.0% (6/20; 95%CI, 9.9%-50.1%) and 4.6% (15/324; 95%CI, 2.3%-6.9%) of FALS and SALS patients, respectively. SOD1 (4/20, 20.0%) and FUS (2/20, 10.0%) account for all mutations in FALS patients, whereas FUS (6/324, 1.9%) and SOD1 (4/324, 1.2%) were most frequent mutated genes, followed by TARDBP (3/324, 0.9%), C9ORF72 (1/324, 0.3%), and ANG (1/324, 0.3%) in SALS patients. Although no mutations were detected in VCP and PFN1, there was an increase in the frequency of the T allele of the rs13204 single nucleotide polymorphism in PFN1 in SALS patients compared with in controls. Patients with FUS mutations were younger at onset (P<0.01) and had shorter lifespan (P<0.01), compared with those without the mutations.

Conclusions CONCLUSIONS: Mutations in major ALS-related genes are present in approximately 30% and 5% of Chinese FALS and SALS patients, respectively. SOD1 and FUS are the only mutated genes in FALS patients and the most frequently mutated genes in SALS patients, which appear to be different from the profiles reported in Caucasian ALS patients. Mutation in ANG is, for the first time, reported in an SALS patient in Asian populations. Moreover, FUS mutations are associated with an early onset and poor prognosis. The results suggest that there is an ethnic difference in the genetic background of ALS.

Authors/Disclosures
Zhangyu Zou, MD, PhD (Fujian Medical University Union Hospital) PRESENTER	No disclosure on file
	No disclosure on file
	No disclosure on file
Liying Cui, PhD (Peking Union Medical College Hospital)	No disclosure on file
Steven E. Arnold, MD (Massachusetts General Hospital)	Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for EIP Pharma. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Eisai. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Sage Therapeutics. Dr. Arnold has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cortexyme. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Boyle Shaughnessy Law. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as an Expert Witness for Wolf Greenfield. Dr. Arnold has received personal compensation in the range of $500-$4,999 for serving as a Advisory Board Member with Bob's Last Marathon.

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