罕见的DNAJC7变异可能在中国ALS患者中起到较小的作用
Shichan Wang1, Xiaoting Zheng1, Qianqian Wei1
1Department of Neurology, Laboratory of Neurodegenerative Disorders, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Chengdu, 610041610041, Sichuan, China.
Molecular neurobiology
|October 23, 2023
概括
DnaJ热冲击蛋白家族成员C7基因 (DNAJC7) 的罕见变异被选在中国肌缩侧面硬化症 (ALS) 患者中. DNAJC7变异与四肢发病和进展缓慢有关,但在ALS病例中没有显著丰富.
科学领域:
- 遗传学 遗传学 是一个
- 神经科学是一个神经科学.
- 分子生物学分子生物学
背景情况:
- 肌缩侧面硬化症 (ALS) 是一种进展性神经退行性疾病.
- DnaJ热冲击蛋白家族成员C7基因 (DNAJC7) 被认为是ALS的遗传风险因素.
- 了解ALS的遗传基础对于开发有效疗法至关重要.
研究的目的:
- 在一个大型的中国ALS患者队伍中,选DNAJC7基因的罕见变异.
- 研究ALS患者的DNAJC7基因变异和临床表型之间的相关性.
- 评估DNAJC7在ALS发病过程中的潜在作用.
主要方法:
- 在2124名中国ALS患者中进行了全外体测序或向基因测序.
- 在DNAJC7基因中发现了罕见的变异 (小等位基因频率<0.1%).
- 使用in silico工具来预测已识别的变种的病原性.
- 分析了基因型-表型相关性,包括疾病发病率和进展率.
- 进行负担分析,以比较ALS患者和对照组之间的变异频率.
主要成果:
- 在2124名ALS患者中发现了4种罕见的DNAJC7变异 (0.19%的频率).
- 其中包括一种蛋白质截断变体和三个误解变体,所有这些变体都被预测是有害的.
- 患有DNAJC7变异的患者倾向于表现出肢体发病的ALS和较慢的疾病进展.
- 负担分析没有显示与对照组相比,ALS患者中罕见的破坏性DNAJC7变异的显著丰富.
结论:
- 虽然在中国的ALS患者中发现了罕见的破坏性DNAJC7变异,并与特定的临床特征相关,但它们在患者队列中没有显著丰富.
- DNAJC7在ALS发病过程中的作用需要对更大,更多样化的群体进行进一步的研究.
- 需要进行额外的研究才能充分阐明DNAJC7对ALS病因学的贡献.
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