南方医科大学学报

南方医科大学学报 ›› 2021, Vol. 41 ›› Issue (1): 75-78.doi: 10.12122/j.issn.1673-4254.2021.01.10

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HSPB1基因罕见变异可能与肌萎缩侧索硬化发病相关

陈君逸，刘向一，徐迎胜，樊东升   

  • 出版日期:2021-01-26 发布日期:2021-01-22

Rare variants of HSPB1 are probably associated with amyotrophic lateral sclerosis

  • Online:2021-01-26 Published:2021-01-22

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摘要：

目的 探讨HSPB1基因罕见变异与肌萎缩侧索硬化（ALS）发病的相关性。方法 对166例中国ALS患者进行二代测序基因检测，筛选出HSPB1基因可能的致病性罕见变异，分别与千人计划及国内全外显子测序健康对照数据库比对分析，进行序列核关联性检验（SKAT）及优化的SKAT（SKAT-O）。结果 本研究共筛选出3个HSPB1基因可能的致病性罕见变异：c.379C>T（p.R127W）、c.446A>C（p.D149A）及c.451A>C（p.T151P），均为错义突变。以千人计划作为对照，SKAT p=3.61×10-7，SKAT-O p=1.62×10-6；以国内全外显子测序健康对照数据库作为对照，SKAT p=9.99×10-4，SKAT-O p=1.80×10-3。未发现该基因罕见变异携带者的特征性临床表型特点。结论 HSPB1基因罕见变异可能与ALS发病存在相关性。

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Abstract:

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. Conclusion Rare variants of HSPB1 are probably associated with the pathogenesis of ALS.

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