TY - DATA T1 - Six SQSTM1 mutations in a Chinese amyotrophic lateral sclerosis cohort PY - 2015/08/27 AU - Yi Yang AU - Lu Tang AU - Nan Zhang AU - Lei Pan AU - Shinji Hadano AU - Dongsheng Fan UR - https://tandf.figshare.com/articles/journal_contribution/Six_SQSTM1_mutations_in_a_Chinese_amyotrophic_lateral_sclerosis_cohort/1582711 DO - 10.6084/m9.figshare.1582711.v1 L4 - https://ndownloader.figshare.com/files/2369133 KW - uba KW - Chinese ALS patients KW - pcr KW - pb KW - fs KW - traf KW - ALS patients KW - E 81K N 239K G 297S E 372D P 388S KW - p.N 239K c .889 G KW - p.E 372D c .1162 C KW - p.G 297S c .1116 G KW - P 392 L KW - SQSTM 1 mutation carriers KW - SQSTM 1 mutation KW - SQSTM 1 mutations KW - c .241 G KW - 471 ALS patients KW - p.E 81K c .717 C KW - SQSTM 1 gene mutations KW - c .1175 C KW - SQSTM 1 gene KW - p 62 function KW - p.P 392 L N2 - The purpose of this study was to identify SQSTM1 gene mutations, estimate survival based on the progression rate of the revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score (ΔFS), and characterize the relationships between SQSTM1 mutations and clinical phenotypes in Chinese ALS patients. We sequenced the SQSTM1 gene in 35 familial ALS patients, 436 sporadic ALS patients, and 384 healthy controls. SQSTM1 gene mutations were screened with PCR and direct sequencing; the correlations between genotype and phenotype and the progressive ALSFRS-R ratio were analyzed. Results revealed six heterozygous missense mutations in 471 ALS patients: c.241 G> A (p.E81K), c.717 C> A (p.N239K), c.889 G> A (p.G297S), c.1116 G> C (p.E372D), c.1162 C> T (p.P388S) and c.1175 C> T (p.P392 L). The gender ratio was 1:1, and the limb was the site of disease onset in mutation-positive patients. Notably, the ΔFS analysis revealed that the risk of death or tracheostomy was significantly increased in SQSTM1 mutation carriers (p < 0.05). In conclusion, E81K, N239K, G297S, E372D, P388S and P392 L were detected in the PB1, TRAF6, PEST and UBA domains, which are important to p62 function and prone to ALS. The incidence of ALS caused by the SQSTM1 mutation has increased from 30 to 35 worldwide. ER -