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浙江大学学报（医学版）
浙江大学学报（医学版）  2018, Vol. 47 Issue (3): 227-238    DOI: 10.3785/j.issn.1008-9292.2018.06.02
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遗传和表观遗传机制在先天性心脏病中的研究进展
田广烽(),高慧,胡莎莎,舒强*()
浙江大学医学院附属儿童医院心胸外科, 浙江 杭州 310052
Research progress on genetic and epigenetic mechanisms in congenital heart disease
TIAN Guangfeng(),GAO Hui,HU Shasha,SHU Qiang*()
Department of Cardiovascular and Thoracic Surgery, the Children's Hospital, Zhejiang University School of Medicine, Hangzhou 310052, China
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摘要：

先天性心脏病是胎儿期心脏及大血管发育异常所致的先天性畸形，是最常见的出生缺陷之一。先天性心脏病病因复杂，染色体异常、基因突变、核酸修饰、非编码RNA等遗传和表观遗传机制在其发生过程中发挥重要作用。现阶段，染色体异常、基因突变等遗传机制已经广泛应用于临床疾病的诊断与治疗。然而，针对遗传及表观遗传修饰在先天性心脏病的诊疗应用仍需深入研究。本文综述了染色体异常、基因突变、拷贝数变异及表观遗传修饰与先天性心脏病发生的关系，以期为进一步探究先天性心脏病早期诊断及个体化治疗提供依据。
关键词： 心脏缺损, 先天性/遗传学;  染色体畸变:组蛋白类/遗传学;  后成说, 遗传;  微RNAs;  DNA甲基化;  综述    
Abstract:

Congenital heart disease (CHD) is a type of birth defects due to the abnormal development of heart and blood vessels during embryonic stage. Studies indicate that the etiology of CHD is complicated. Genetic and epigenetic mechanisms including chromosomal abnormalities, gene mutations, nucleic acid modifications, non-coding RNAs may play important roles in CHD. At present, genetic mechanisms such as chromosome abnormality and gene mutation have been widely used in the diagnosis and treatment of clinical diseases. However, the application of genetic and epigenetic modification in diagnosis and treatment of CHD still need further research. This paper reviews the relationship between chromosomal abnormality, gene mutation, copy number variation, epigenetic modification and the occurrence of CHD, which may provide a basis for further exploring the early diagnosis and individualized therapy of CHD.
Key words: Heart defects, congenital/genetics    Chromosome aberrations    Histones/genetics    Epigenesis, genetic    MicroRNAs    DNA methylation    Review
收稿日期: 2018-02-23 出版日期: 2018-09-18
CLC:  R722.11  
基金资助: 浙江省重点研发计划(2017C03009);浙江省卫生高层次人才培养工程(2016-6)
通讯作者: 舒强     E-mail: guangfeng_tian@zju.edu.cn;shuqiang@zju.edu.cn
作者简介: 田广烽(1992-), 男, 硕士研究生, 主要从事出生缺陷防治研究; E-mail:guangfeng_tian@zju.edu.cn; https://orcid.org/0000-0002-9242-8789
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引用本文:

田广烽,高慧,胡莎莎,舒强. 遗传和表观遗传机制在先天性心脏病中的研究进展[J]. 浙江大学学报（医学版）, 2018, 47(3): 227-238.

TIAN Guangfeng,GAO Hui,HU Shasha,SHU Qiang. Research progress on genetic and epigenetic mechanisms in congenital heart disease. J Zhejiang Univ (Med Sci), 2018, 47(3): 227-238.

链接本文:

http://www.zjujournals.com/med/CN/10.3785/j.issn.1008-9292.2018.06.02    或    http://www.zjujournals.com/med/CN/Y2018/V47/I3/227

图 1  遗传和环境因素与先天性心脏病发生的关系
基因 心脏表型 参考文献
ACTC1 房间隔缺损、室间隔缺损 [17]
ACVR2B 心脏左右轴异位畸形 [18]
ALK2 房间隔缺损 [19]
AXIN2 先天性瓣膜缺损 [20]
ANKRD1 总静脉回流异常 [21]
BAF60C 房间隔缺损、室间隔缺损、房室间隔缺损、心脏圆锥动脉畸形 [22]
BRAF 肺动脉狭窄、房间隔缺损 [23]
BRG1 房间隔缺损、室间隔缺损 [24]
CHD7 法洛四联症、右室双向流出道 [25]
CITED2 房间隔缺损、室间隔缺损 [26]
CRELD1 房室间隔缺损 [27-29]
CX40 心室发育不良 [30]
CX43 法洛四联症 [31]
DLC1 房间隔缺损 [32]
ELN 上腔静脉主动脉狭窄 [33]
FOXH1 法洛四联症、先天性心功能异常 [34]
GATA4 房间隔缺损、房室间隔缺损、法洛四联症 [35-38]
GATA6 持续性动脉硬化性肺动脉瓣 [39]
GDF1 法洛四联症、大动脉转位 [19]
GJA5 室间隔缺损、法洛四联症、主动脉狭窄 [40-41]
HAND2 法洛四联症 [42-43]
HDAC5 室间隔缺损 [44]
HEY2 三尖瓣闭锁 [45]
HRAS IRX4 肺动脉狭窄、心动过速室间隔缺损 [46][47]
JAG1 法洛四联症 [48-49]
KRAS 肺动脉狭窄、房间隔缺损 [50]
MAP2K1 肺动脉狭窄、房间隔缺损 [51]
MED13L 大动脉转位、左心发育不良、主动脉狭窄 [52]
MYBPC3 房间隔缺损、室间隔缺损 [53-55]
MEF2C 室间隔缺损 [56]
MESP1 右室双向流出道 [57]
MYH6 房间隔缺损 [58]
MYH7 左心室心肌致密化不全、二叶式主动脉 [59]
NKX2.5 房间隔缺损、室间隔缺损、法洛四联症、右室双向流出道、左心发育不全 [60-64]
NKX2.6 持续性动脉硬化性肺动脉瓣 [65]
NODAL 大动脉转位 [66-69]
NOTCH1 主动脉瓣疾病 [67-68]
NOTCH2 法洛四联症、肺动脉狭窄、主动脉狭窄 [69]
NR2F2 房间隔缺损、主动脉狭窄 [70]
PTPN11 房间隔缺损、室间隔缺损、肺动脉狭窄 [71]
RAF1 房间隔缺损、法洛四联症 [72]
PAX2 室间隔缺损 [73]
RIT1 室间隔缺损、法洛四联症、主动脉狭窄 [74]
SEMA3E 法洛四联症、右室双向流出道 [75]
SMAD6 主动脉瓣疾病 [76]
SMYD1 心室发育不良 [77]
SOS1 房间隔缺损、室间隔缺损、法洛四联症 [78]
SOX9 法洛四联症 [79]
STRT1 房间隔缺损、室间隔缺损 [80]
TBX1 室间隔缺损、主动脉弓中断 [81-83]
TBX5 房间隔缺损、室间隔缺损、房室间隔缺损 [84]
TBX20 房间隔缺损、室间隔缺损、左心发育不良、动脉导管未闭 [85-86]
TDGF1 法洛四联症 [34]
WHSC1 房间隔缺损、室间隔缺损 [87]
ZFPM2 法洛四联症、右室双向流出道 [88]
ZIC3 房间隔缺损、大动脉异位 [89-91]
表 1  与先天性心脏病相关的基因及其表型
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