短串联重复序列相关神经肌肉病临床及机制研究进展

doi:10.3969/j.issn.1672-6731.2023.09.002

摘要/Abstract

摘要：

短串联重复序列（STR）是人类基因组的构成部分，其重复次数易在DNA复制过程中发生变化，当重复次数超过一定阈值时可导致疾病的发生，其中大多数累及神经系统。随着第三代长读长测序技术的迅速发展和广泛应用，越来越多的神经肌肉病被证实与STR异常扩增有关。本文综述STR相关神经肌肉病的临床和机制研究进展，以为临床研究提供指导。

关键词: 神经肌肉疾病, 微卫星重复, 综述

Abstract:

Short tandem repeat (STR) is a component of the human genome, the number of repeats of STR is prone to change during DNA replication, and when it exceeds a certain threshold, it will lead to the occurrence of diseases, most of which involve the nervous system. With the rapid development and wide application of the third generation long read long sequencing technology, more and more neuromuscular diseases have been confirmed to be related to STR variation. This article reviews the clinical and mechanism research progress on STR-related neuromuscular diseases, so as to provide guidance for clinical research.

Key words: Neuromuscular diseases, Microsatellite repeats, Review

万雅兰, 于佳希, 邓健文, 洪道俊, 王朝霞. 短串联重复序列相关神经肌肉病临床及机制研究进展[J]. 中国现代神经疾病杂志, 2023, 23(9): 775-781.

Ya-lan WAN, Jia-xi YU, Jian-wen DENG, Dao-jun HONG, Zhao-xia WANG. Clinical and mechanism research progress on short tandem repeat-related neuromuscular diseases[J]. Chinese Journal of Contemporary Neurology and Neurosurgery, 2023, 23(9): 775-781.

https://journal11.magtechjournal.com/cjcnn/CN/Y2023/V23/I9/775

图/表 1

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疾病名称	致病基因	重复序列区域	重复序列	发病年龄	临床特征
OPDM	LRP12	5’UTR	CGG	成年早期发病	慢性进行性双侧上睑下垂、眼外肌麻痹、面肌无力、咽喉部症状以及远端肢体受累
	GIPC1	5’UTR	CGG
	NOTCH2NLC	5’UTR	CGG
	RILPL1	5’UTR或外显子区	CGG
NIID-M	NIOTCH2NLC	5’UTR	CGG	成年期发病	成年期发病的肢体肌无力，伴或不伴眼外肌、面肌、咽喉肌无力，可伴脑白质病变
OPML	LOC6423	5’UTR	CGG	青少年至成年早期发病	上睑下垂、眼球活动受限、吞咽困难、构音障碍、四肢肌无力，大脑萎缩以及皮髓质交界处白质高信号
KD	AR	外显子区	CAG	中年期发病	肢体近端骨骼肌和舌肌慢性进行性无力、肌萎缩，常伴姿势性震颤、感觉异常、自主神经损害及内分泌异常（男性乳房发育、睾丸萎缩、生殖能力下降）
OPMD	PABPN1	外显子区	GCN	中年期发病	缓慢进行性上睑下垂、吞咽困难、构音障碍和肢体近端肌无力上下运动神经元损伤，常伴痴呆
ALS/FTD	HTT	外显子区	CAG	中老年期发病
	NIPA1	外显子区	GCG	中老年期发病
	ATXN2	5’UTR	CAG	中老年期发病
	C9orf72	内含子区	GGGGCC	中年期发病
CANVAS	RFC1	内含子区	AAGGG	中老年期发病	小脑性共济失调、前庭功能减退和非长度依赖性感觉神经病，病情进展缓慢，可伴自主神经病变、慢性咳嗽
DM2型	CNBP	内含子区	CCTG	成年期发病	主要以肌强直及肌无力为主，肌肉受累以肢体近端显著，常伴弥漫性肌肉疼痛
DM1型	DMPK	3’UTR	CTG	各年龄段均可发病	肌强直、肌无力和早发白内障（三联征），肢体远端、面肌、咀嚼肌受累，可合并心脏、呼吸系统、消化系统、内分泌系统、中枢神经系统受累

疾病名称	致病基因	重复序列区域	重复序列	发病年龄	临床特征
OPDM	LRP12	5’UTR	CGG	成年早期发病	慢性进行性双侧上睑下垂、眼外肌麻痹、面肌无力、咽喉部症状以及远端肢体受累
	GIPC1	5’UTR	CGG
	NOTCH2NLC	5’UTR	CGG
	RILPL1	5’UTR或外显子区	CGG
NIID-M	NIOTCH2NLC	5’UTR	CGG	成年期发病	成年期发病的肢体肌无力，伴或不伴眼外肌、面肌、咽喉肌无力，可伴脑白质病变
OPML	LOC6423	5’UTR	CGG	青少年至成年早期发病	上睑下垂、眼球活动受限、吞咽困难、构音障碍、四肢肌无力，大脑萎缩以及皮髓质交界处白质高信号
KD	AR	外显子区	CAG	中年期发病	肢体近端骨骼肌和舌肌慢性进行性无力、肌萎缩，常伴姿势性震颤、感觉异常、自主神经损害及内分泌异常（男性乳房发育、睾丸萎缩、生殖能力下降）
OPMD	PABPN1	外显子区	GCN	中年期发病	缓慢进行性上睑下垂、吞咽困难、构音障碍和肢体近端肌无力上下运动神经元损伤，常伴痴呆
ALS/FTD	HTT	外显子区	CAG	中老年期发病
	NIPA1	外显子区	GCG	中老年期发病
	ATXN2	5’UTR	CAG	中老年期发病
	C9orf72	内含子区	GGGGCC	中年期发病
CANVAS	RFC1	内含子区	AAGGG	中老年期发病	小脑性共济失调、前庭功能减退和非长度依赖性感觉神经病，病情进展缓慢，可伴自主神经病变、慢性咳嗽
DM2型	CNBP	内含子区	CCTG	成年期发病	主要以肌强直及肌无力为主，肌肉受累以肢体近端显著，常伴弥漫性肌肉疼痛
DM1型	DMPK	3’UTR	CTG	各年龄段均可发病	肌强直、肌无力和早发白内障（三联征），肢体远端、面肌、咀嚼肌受累，可合并心脏、呼吸系统、消化系统、内分泌系统、中枢神经系统受累

[1]	佟志勇. 颅内动脉瘤与脑血管重建术[J]. 中国现代神经疾病杂志, 2024, 24(8): 595-598.
[2]	佟志勇. 脑血管重建术历史沿革[J]. 中国现代神经疾病杂志, 2024, 24(8): 599-605.
[3]	金凌骥, 胡俊文, 李寅, 王林. 复杂颅内动脉瘤的颅内-颅内血管搭桥术[J]. 中国现代神经疾病杂志, 2024, 24(8): 606-612.
[4]	刘佩玺, 史源, 朱巍. 血流导向时代颅内全域脑血管搭桥术治疗颅内动脉瘤之应用方略[J]. 中国现代神经疾病杂志, 2024, 24(8): 613-618.
[5]	张峰, 孟凡刚. 帕金森病自主神经功能障碍丘脑底核脑深部电刺激术治疗进展[J]. 中国现代神经疾病杂志, 2024, 24(7): 510-515.
[6]	吴桂智, 田宏. Meige综合征脑深部电刺激术治疗进展[J]. 中国现代神经疾病杂志, 2024, 24(7): 516-521.
[7]	孟凡刚, 张建国. 耳后磨骨槽技术在脑深部电刺激术中的应用[J]. 中国现代神经疾病杂志, 2024, 24(7): 522-524.
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[10]	史若琳, 高秀洁, 崔家宁, 邵妍, 谢璐霜, 刘毅. 5-羟色胺与帕金森病非运动症状研究进展[J]. 中国现代神经疾病杂志, 2024, 24(6): 497-501.
[11]	李海峰. 在进入靶向治疗的时代激素仍然是重症肌无力治疗的基础[J]. 中国现代神经疾病杂志, 2024, 24(5): 295-307.
[12]	许鸿嘉, 舒崖清, 王蘋, 李蕃, 许顺良, 邱伟, 马晓宇. 抗水通道蛋白4抗体阳性视神经脊髓炎谱系疾病诊断与治疗进展[J]. 中国现代神经疾病杂志, 2024, 24(5): 308-314.
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2 短串联重复序列相关神经肌肉病临床及机制研究进展

Clinical and mechanism research progress on short tandem repeat-related neuromuscular diseases

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