二代测序技术在血管性血友病诊断中的应用

doi:10.3969/j.issn.1004-583X.2022.09.019

摘要/Abstract

摘要：

血管性血友病(von Willebrand disease, VWD)是最常见的遗传出血性疾病,临床表现异质性大,出血严重时可危及患者生命。快速、精准的诊断有助于疾病的治疗。目前,实验室检测仍是VWD诊断的主要手段,但突变基因的低外显率、实验室的高变异性和大量影响血管性血友病因子(von Willebrand factor, VWF)水平测定的干扰因素使诊断变得复杂,甚至误诊。近年来,二代测序技术(next-generation sequencing,NGS)已应用于临床,并且具有高通量、高灵敏度、价格低廉等优点,可准确发现VWF基因缺陷,现已成为诊断VWD的有效手段之一。本文就NGS在VWD诊断中的应用进行综述,旨在为临床诊断提供依据。

中图分类号:

R554.9

杨文, 周泽平. 二代测序技术在血管性血友病诊断中的应用[J]. 临床荟萃, 2022, 37(9): 860-864.

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链接本文: https://huicui.hebmu.edu.cn/CN/10.3969/j.issn.1004-583X.2022.09.019

https://huicui.hebmu.edu.cn/CN/Y2022/V37/I9/860

图/表 2

参考文献 30

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VWD 类型	遗传模式	实验室检测					外显子变异位置	结构域变异位置	致病机制	热点突变
VWD 类型	遗传模式	VWF:Ag	VWF:RCo	FVIII:C	VWF:RCo/ VWF:Ag	RIPA	外显子变异位置	结构域变异位置	致病机制	热点突变
1	AD	↓	↓	N/↓	>0.7	↓	1~52	全部	VWF的合成或分泌受影响;血浆VWF的清除加快	C2257S,L2207P,W1144G,I1415N等
2A	AD,AR	↓↓	↓	N/↓	<0.7	↓	2~28, 51~52	A1,A2	VWF对ADAMTS13 水解酶敏感性增加	S1506L,Y1605S,R1597W等
								D',D3,	VWF在胞内滞留	C1149R等
								D1,D2,CK	VWF多聚化受影响	E248G等
2B	AD	↓↓	↓	N/↓	<0.7	↑	28	A1	血小板清除率增加;高分子量VWF多聚体丢失	R1306W,R1308C,V1316M,R1341Q等
2M	AD	↓	↓	N/↓	<0.7	↓	28~32	A1,A2, A3	VWF与血小板的黏附能力减弱	204delC,S1387I等
2N	AR	N	N	↓	>0.7	N	17~27	D2,D',D3	FVIII失去保护被降解	R760C,R763G,Y795C,C788Y等
3	AR	↓↓↓	↓↓↓	↓↓↓	-	↓↓↓	1~52	全部	VWF在胞内滞留;基因缺失干扰VWF的正确折叠和生物合成	R1659X,S85P,C2671Y,C2739Y等

VWD 类型	遗传模式	实验室检测					外显子变异位置	结构域变异位置	致病机制	热点突变
VWD 类型	遗传模式	VWF:Ag	VWF:RCo	FVIII:C	VWF:RCo/ VWF:Ag	RIPA	外显子变异位置	结构域变异位置	致病机制	热点突变
1	AD	↓	↓	N/↓	>0.7	↓	1~52	全部	VWF的合成或分泌受影响;血浆VWF的清除加快	C2257S,L2207P,W1144G,I1415N等
2A	AD,AR	↓↓	↓	N/↓	<0.7	↓	2~28, 51~52	A1,A2	VWF对ADAMTS13 水解酶敏感性增加	S1506L,Y1605S,R1597W等
								D',D3,	VWF在胞内滞留	C1149R等
								D1,D2,CK	VWF多聚化受影响	E248G等
2B	AD	↓↓	↓	N/↓	<0.7	↑	28	A1	血小板清除率增加;高分子量VWF多聚体丢失	R1306W,R1308C,V1316M,R1341Q等
2M	AD	↓	↓	N/↓	<0.7	↓	28~32	A1,A2, A3	VWF与血小板的黏附能力减弱	204delC,S1387I等
2N	AR	N	N	↓	>0.7	N	17~27	D2,D',D3	FVIII失去保护被降解	R760C,R763G,Y795C,C788Y等
3	AR	↓↓↓	↓↓↓	↓↓↓	-	↓↓↓	1~52	全部	VWF在胞内滞留;基因缺失干扰VWF的正确折叠和生物合成	R1659X,S85P,C2671Y,C2739Y等

二代测序技术在血管性血友病诊断中的应用

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