肝豆状核变性的基因诊断研究进展

摘要/Abstract

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R742.4

姚碧莲, 张欣欣, 韩悦. 肝豆状核变性的基因诊断研究进展[J]. 内科理论与实践, 2021, 16(05): 354-358.

图/表3

图1

表1

ATP7B突变与临床表型

突变类型	临床表现特点	参考文献
p.R778L	发病年龄早,铜蓝蛋白及血清铜水平低	[ 21 ]
p.R919G	神经系统症状为主,铜蓝蛋白水平较高	[ 21 ]
p.T935M	同时具有神经系统和肝脏病变,铜蓝蛋白水平较高	[ 21 ]
p.L492S、p.V519M、p.E541K、p.L549P、p.A604P、p.R616W、p.P992L、p.N1270S	发病年龄较早	[ 32 ]
p.I1148T	12岁后发病	[ 32 ]
p.M769Hfs*26	肝脏疾病症状表现较多	[ 33 ]
p.H1069Q/ p.M769Hfs*26	构音障碍及吞咽困难等症状表现较多	[ 33 ]
p.A1003T	神经系统疾病密切相关	[ 18 ]
p.S653Y	铜蓝蛋白水平正常	[ 34 ]
移码突变、无义突变、缺失突变	铜蓝蛋白水平低	[ 34 ]
大片段缺失突变	发病年龄早,多存在较为严重的肝脏病变（如进行性肝炎、肝硬化、肝衰竭）	[ 36 ]

表1

表2

修饰基因突变与临床表型

修饰基因	突变位点	临床表型	参考文献
COMMD1	p.D164D	神经和肝脏症状早发	[ 40 ]
SOD2	p.V16A	男性发病早	[ 40 ]
CAT	c.262C>T	男性发病晚	[ 40 ]
BDNF	p.Y90Y	平均发病年龄推迟	[ 41 ]
ApoE	ε3基因型 ε4基因型	发病较晚女性患者临床症状表现早	[ 42 - 43 ] [ 45 ]
PRNP	p.M129V	与神经系统表型相关	[ 44 ]
ESD		增加神经症状风险	[ 45 ]
染色体重塑因子INO80		降低神经症状风险	[ 45 ]
ATOX1	5'UTR-99 T>C	发病较早	[ 46 ]
XIAP	p.T470S p.N340S	发病较早	[ 47 ]
PNPLA3	rs738409	与中/重度肝脏脂肪变相关	[ 48 ]
MTHFR	667T 1298C	与肝脏表型相关发病年龄较早	[ 49 ]

表2

参考文献50

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肝豆状核变性的基因诊断研究进展

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