在ALS和其他神经退行性或神经肌肉疾病之间存在遗传重叠
Cathrine Goberg Olsen1,2, Øyvind Løvold Busk1, Øystein Lunde Holla1
1Department of Medical Genetics, Telemark Hospital Trust, Skien, Norway.
Amyotrophic lateral sclerosis & frontotemporal degeneration
|October 18, 2023
概括
与其他神经疾病相关的遗传变异,特别是在NEK1中,在9%的肌缩侧面硬化症 (ALS) 患者中发现. 许多人缺乏家族史,这表明ALS的更广泛的遗传联系.
科学领域:
- 神经遗传学 神经遗传学
- 神经肌肉疾病 神经肌肉疾病
- 神经退行性疾病 神经退行性疾病
背景情况:
- 在挪威 (89%的病例),肌缩侧面硬化症 (ALS) 诊断往往不是遗传的.
- 与ALS相关的基因与导致其他神经肌肉和神经退行性疾病的基因有显著的重叠.
- 了解遗传基础对于诊断和潜在治疗ALS至关重要.
研究的目的:
- 调查ALS患者神经系统疾病家族病史的患病率.
- 在ALS患者中识别与其他神经退行性或神经肌肉疾病相关的罕见遗传变异.
- 探索可能导致ALS的新型遗传因素.
主要方法:
- 基于人口的279名挪威ALS患者队列.
- 对510个相关基因的外体序列测序和生物信息学分析.
- 变体解释的基因型-表型相关性.
主要成果:
- 31%的ALS患者有亲属患有其他神经退行性疾病 (例如痴呆症,帕金森病).
- 在25名患者 (9%的队列) 中发现了NEK1,KIF1A和LRRK2等基因的20种潜在致病变体.
- 在ALS队列中,NEK1变异存在于2.5%;大多数患有这些变异的患者没有相关的家族病史.
结论:
- 与其他神经退行性/神经肌肉疾病相关的罕见遗传变异在相当一部分ALS患者中存在.
- 在像NEK1这样的基因中频繁识别变异突出了它们在ALS中的潜在作用.
- 作为潜在的ALS相关基因,AFG3L2,ATP7A,BICD2,KIF1A和MSTO1需要进一步调查.
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