[1]谭文婷,向密,但芸婕,等.119例肝豆状核变性临床特征及致病基因ATP7B变异谱分析[J].第三军医大学学报,2018,40(18):1674-1681.
 TAN Wenting,XIANG M,DAN Yunjie,et al.Clinical characteristics and mutation spectrum of the pathogenic gene ATP7B in Chinese patients with Wilson’s disease: analysis of 119 cases[J].J Third Mil Med Univ,2018,40(18):1674-1681.
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119例肝豆状核变性临床特征及致病基因ATP7B变异谱分析(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第18期
页码:
1674-1681
栏目:
临床医学
出版日期:
2018-09-30

文章信息/Info

Title:
Clinical characteristics and mutation spectrum of the pathogenic gene ATP7B in Chinese patients with Wilson’s disease: analysis of 119 cases
作者:
谭文婷向密但芸婕郭衍志向小梅朱研胡俊邓国宏
陆军军医大学(第三军医大学)第一附属医院:感染科,神经内科
Author(s):
TAN Wenting XIANG M1 DAN Yunjie GUO Yanzhi XIANG Xiaomei ZHU Yan HU Jun DENG Guohong

Infectious Diseases Department of Neurology, First Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400038, China
 

关键词:
肝豆状核变性临床特征ATP7B基因肝型脑型
分类号:
R3921-33;R394.3;R596.1
文献标志码:
A
摘要:

目的     探讨肝豆状核变性的临床特征及其致病基因ATP7B的中国人群变异谱。方法     收集2011年1月-2017年10月我院肝豆状核变性119例,随访至2018年4月,分析发病年龄、临床特征、生化指标、ATP7B基因变异谱及转归,比较肝型和脑型患者的差异。结果     119例患者中肝型占57.1%,脑型占27.7%,混合型占15.1%。肝型与脑型患者发病年龄差异有统计学意义(P=00036),脑型患者全部集中在儿童青少年期起病,肝型患者各年龄段均有发病。本组患者肝损害主要表现为肝功能异常(53.8%)、肝硬化(50.4%)、肝脾肿大(47.9%)和皮肤巩膜黄染(40.3%);神经系统损伤主要表现为口下颌肌张力障碍(31.9%)、精神症状(24.4%)和不自主运动(23.5%);成年患者的肝硬化、腹水、不自主运动等症状显著多于未成年患者(分别为:P=0.005、0.008、0.026)。对诊断时效进行分析,从首次发病至明确诊断中位病程为5个月,最长82个月,52.1%的患者在起病5个月之后才得以明确诊断,肝型患者确诊所用时间显著少于脑型和混合型患者(分别为:Z=-2.233,P=0.026;Z=-2.424,P=0.015)。31例患者进行ATP7B基因检测,阳性率83.9%,最常见致病变异位点是Arg778Leu,等位频率17.4%,其次是Pro992Leu、Met769HisfsX26、Ala874Val和Ile1148Thr。生存分析结果显示,有肝硬化的肝豆状核变性患者的生存率显著低于非肝硬化患者(χ2=4.202,P=0.04)。结论     婴幼儿及中老年人发病并不少见,应重视年幼和年老患者的诊治;进展为肝硬化的患者因铜沉积久、肝损伤重,其生存率显著低于非肝硬化患者,而基因检测有助于提高早期诊断率。

Abstract:

Objective    To investigate the clinical and molecular characteristics of Wilson’s disease (WD) in Chinese patients.  Methods     The clinical data were retrospectively collected from 119 Chinese patients with WD admitted in our hospital between January, 2011 and October, 2017. All the patients were followed up to April, 2018, and the age of disease onset, clinical characteristics, biochemical profiles, mutation spectrum of the pathogenic gene ATP7B, and outcomes were analyzed comparatively between the patients with neurological and hepatic subtypes.  Results     Among the 119 patients, diagnoses of hepatic subtype of WD were established in 68 (57.1%) patients, neurological subtype in 33 (27.7%) patients and mix subtype in 18 (15.1%) patients. The age of disease onset was significantly different between the neurological and hepatic subtypes (P=0.003 6); the neurological subtype occurred mostly in children and adolescents (from 8 to 40 years old) while the hepatic subtype could occur in all age ranges (1 to 58 years old). The common hepatic manifestations of AD included abnormal liver functions (53.8%), cirrhosis (50.4%), hepatosplenomegaly (47.9%) and jaundice (75.9%), while the neurological manifestations included oromandibular dystonia (31.9%), psychiatric symptoms (24.4%) and involuntary movements (23.5%). Compared with the juvenile patients, the adult patients had significantly higher incidences of liver cirrhosis (P=0.005), ascites (P=0.008) and involuntary movements (P=0.026). In the overall patients, the median interval between disease onset and a confirmed diagnosis was 5 months, and the longest interval could reach 6.8 years; the interval between disease onset and diagnosis was significantly shorter in patients with the hepatic subtype than in those with the neurological subtype (Z=-2.233, P=0.026) and the mixed subtype (Z=-2.424, P=0.015). ATP7B gene sequencing was carried out in 31 cases, and 83.9% of them were found positive for gene mutations. The common mutation sites included p.Arg778Leu (17.4%), p.Pro992Leu (6.8%), Met769HisfsX26 (4.8%), p.Ala874Val (4.8%) and p.Ile1148Thr (4.8%). Survival analysis showed that WD patients with cirrhosis had a significantly lower survival rate than the non-cirrhotic patients (Chisquare=4.202, P=0.04). Conclusion      WD is not uncommon in children and middle-aged individuals, which urges an increased awareness of WD in these populations. This disease is particularly severe in cirrhotic patients, who often have a lowered survival rate compared to the non-cirrhotic patients. For a highly suspected case, ATP7B gene detection can be helpful to obtain an early diagnosis.

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更新日期/Last Update: 2018-09-29