[Rare variants of HSPB1 are probably associated with amyotrophic lateral sclerosis].

OBJECTIVE:To explore the association between rare HSPB1 variants and amyotrophic lateral sclerosis (ALS). METHODS:We performed next-generation sequencing for 166 Chinese ALS patients to screen for possible pathogenic rare variants of HSPB1. The control individuals were obtained from 1000 Genome Project and an in-house whole-exome sequencing database. The Sequence Kernel Association Test (SKAT) and the SKAT-optimal test (SKAT-O) were used to identify the association between rare HSPB1 variants and ALS. RESULTS:We identified 3 possible pathogenic rare variants of HSPB1 (all were missenses), including c.379C>T (p.R127W), c.446A>C (p.D149A) and c.451A>C (p.T151P). Compared with 1000 Genome Project, SKAT p=3.61×10-7 and SKAT-O p=1.62×10-6; while compared with the in-house database, SKAT p=9.99×10-4, SKAT-O p= 1.80×10-3. We analyzed the phenotypes of rare HSPB1 variant carriers and found no specific clinical characteristics associated with these variants. CONCLUSIONS:Rare variants of HSPB1 are probably associated with the pathogenesis of ALS.