RNA结合基序蛋白20相关心肌病的研究进展

孙肖云; 申阳; 洪葵

doi:10.13201/j.issn.1001-1439.2023.10.006

RNA结合基序蛋白20相关心肌病的研究进展

- 1.
  南昌大学第二附属医院医学遗传科(南昌，330006)
- 2.
  江西省分子医学重点实验室
- 3.
  南昌大学第二附属医院心血管内科
基金项目:
国家自然科学基金项目(No：31860320)；江西省青年科学基金项目(No：20181BAB215030)

详细信息

通讯作者: 申阳，E-mail：sain.yong@gmail.com

中图分类号: R542.2

收稿日期: 2022-11-18

刊出日期: 2023-10-13

The progress of RBM20 related cardiomyopathy

- 1.
  Department of Medical Genetics, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
- 2.
  Jiangxi Key Laboratory of Molecular Medicine
- 3.
  Department of Cardiology, The Second Affiliated Hospital of Nanchang University

More Information

Corresponding author: SHEN Yang, E-mail: sain.yong@gmail.com

Received Date: 18 November 2022

Publish Date: 13 October 2023

摘要

摘要: 扩张型心肌病(DCM)是临床常见的原发性心肌病之一，是造成心脏性猝死的重要原因，至今已报道51个相关致病基因。不同基因导致的DCM亚型具有特异性临床特征与遗传异质性。其中RNA结合基序蛋白20(RNA-binding motif protein 20，RBM20)编码心肌特异性mRNA剪接调节因子，是DCM明确致病基因之一。RBM20基因相关DCM具有遗传外显率高、发病年龄早、心脏猝死率高等严重临床表现。其独特的致病分子机制也显示出其作为心力衰竭潜在治疗靶点的可能性。本文将对RBM20相关DCM的发病机理、分子遗传学、临床特征与治疗进行进展性综述，对于DCM亚型的研究强调了基因检测在心血管精准医疗中的重要性。
- 扩张型心肌病 /
- RNA结合基序蛋白20 /
- RNA结合蛋白 /
- 基因检测
Abstract: Dilated cardiomyopathy(DCM) is one of the common inherited cardiomyopathies and an important cause of sudden cardiac death. Up to date, 51 DCM-related genes have been reported. Different gene-related DCM subtypes have specific clinical characteristics and genetic heterogeneity. Among them, the gene of RNA-binding motif protein 20(RBM20) encodes myocardium specific mRNA splicing regulator, which is one of the definitive pathogenic genes of DCM. RBM20-related DCM presents severe clinical manifestations such as high genetic penetrance, early onset age and high rate of sudden cardiac death. The unique pathogenic molecular mechanism of RBM20 also implies its potential as a therapeutic target for heart failure. This review will conclude the pathogenesis, pathology, molecular genetics, clinical features, and treatment of RBM20-associated dilated cardiomyopathy. The research on DCM subtype emphasizes the importance of genetic testing in cardiovascular precision medicine.
- dilated cardiomyopathy /
- RNA-binding motif protein 20 /
- RNA-binding protein /
- genetic testing

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图 1 RBM20基因与蛋白的结构示意图

Figure 1. Structure diagram of RBM20 gene and protein

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表 1 已报道的DCM相关RBM20变异

Table 1. Reported RBM20 variants associated DCM

序号	转录本	cDNA改变	氨基酸改变	外显子	蛋白功能域	ACMG 变异解读	ACMG 评分	参考文献
1	NM_001134363.1	c.247C>A	p.L83I	2	富亮氨酸结构域	致病意义不明变异	2	[25]
2	NM_001134363.1	c.1364C>T	p.S455L	4	-	良性变异	-8	[25]
3	NM_001134363.3	c.1603G>A	p.V535I	6	RRM	致病意义不明变异	0	[13, 21]
4	NM_001134363.3	c.1607T>C	p.I536T	6	RRM	致病意义不明变异	2	[31]
5	NM_001134363.3	c.1898C>T	p.P633L	9	RS结构域	致病意义不明变异	2	[45-46]
6	NM_001134363.1	c.1901G>A	p.R634Q	9	RS结构域	致病变异	13	[4, 8, 21, 47]
7	NM_001134363.3	c.1900C>T	p.R634W	9	RS结构域	致病变异	14	[3, 48-50]
8	NM_001134363.3	c.1903T>G	p.S635A	9	RS结构域	可能致病变异	8	[13]
9	NM_001134363.3	c.1906C>T	p.R636C	9	RS结构域	可能致病变异	8	[21, 51]
10	NM_001134363.3	c.1907G>A	p.R636H	9	RS结构域	致病变异	12	[4, 21, 51-53]
11	NM_001134363.1	c.1906C>A	p.R636S	9	RS结构域	致病变异	15	[4, 13, 54]
12	NM_001134363.1	c.1909A>G	p.S637G	9	RS结构域	可能致病变异	8	[4, 55-56]
13	NM_001134363.3	c.1913C>T	p.P638L	9	RS结构域	致病变异	14	[4, 8, 57-60]
14	NM_001134363.1	c.2109G>T	p.R703S	9	-	致病意义不明变异	1	[25]
15	NM_001134363.3	c.2147G>A	p.R716Q	9	-	致病意义不明变异	1	[21, 53, 59, 61]
16	NM_001134363.3	c.2347A>G	p.R783G	9	-	致病意义不明变异	1	[17]
17	NM_001134363.1	c.2662G>A	p.D888N	11	富谷氨酸结构域	良性变异	-8	[25, 53]
18	NM_001134363.3	c.2737G>A	p.E913K	11	富谷氨酸结构域	致病变异	10	[8, 47, 57, 62]
19	NM_001134363.3	c.2741T>C	p.V914A	11	富谷氨酸结构域	致病意义不明变异	2	[18]
20	NM_001134363.1	c.3091G>T	p.G1031*	11	-	致病变异	10	[3, 25]
21	NM_001134363.1	c.3242C>G	p.P1081R	11	-	致病意义不明变异	0	[25]
22	NM_001134363.1	c.3545G>A	p.R1182H	13	ZnF-2	可能良性变异	-4	[25]
23	NM_001134363.1	c.3616G>A	p.E1206K	14	ZnF-2	致病意义不明变异	0	[25]
RRM：RNA识别基序结构域；RS结构域：富含丝氨酸和精氨酸结构域；ZnF-2：第2个锌指结构域。

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