安徽省337例肝豆状核变性患者临床表型和ATP7B基因变异特征分析  

Analysis of clinical phenotype and ATP7B variants characteristics of 337 patients with hepatolenticular degeneration in Anhui province

作　　者：张士杰 杨文明[2] 杨玉龙 王久香 何伟 Zhang Shijie;Yang Wenming;Yang Yulong;Wang Jiuxiang;He Wei(Experimental Center of Clinical Research,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China;Department of Neurology,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China)

机构地区：[1]安徽中医药大学第一附属医院临床研究实验中心,合肥230031 [2]安徽中医药大学第一附属医院脑病中心,合肥230031

出　　处：《中华医学杂志》2025年第15期1172-1176,共5页National Medical Journal of China

基　　金：国家自然科学基金区域创新发展联合基金(U22A20366);安徽省教育厅重点项目(2023AH050837);安徽省中医药科技攻关专项(202303a07020004)。

摘　　要：目的分析安徽省肝豆状核变性(HLD)患者的临床表型和ATP7B基因变异特征。方法回顾性分析2016年9月至2019年8月在安徽中医药大学第一附属医院确诊为HLD的安徽籍患者(337例),收集其发病症状、发病年龄、诊断年龄、血清铜蓝蛋白水平、角膜K-F环状态以及ATP7B基因变异信息。根据患者发病特征将其分为肝型、脑型、无症状型和其他型,比较肝型和脑型患者的临床表型差异以及常见基因型患者的发病年龄情况。结果337例患者中男213例,女124例,发病年龄2.0~62.6(15.9±9.5)岁,其中肝型89例(26.4%),脑型171例(50.7%),无症状型68例(20.2%),其他类型9例(2.7%)。肝型和脑型患者性别比例、发病年龄、诊断年龄、铜蓝蛋白水平以及角膜K-F环阳性率比较差异均无统计学意义(均P>0.05)。共检测出ATP7B基因突变109种,其中最常见的为c.2333G>T(p.R778L)、c.2975C>T(p.P992L)和c.2621C>T(p.A874V),等位基因频率分别为33.1%、15.7%和3.9%。在296例检出≥2个ATP7B基因变异的患者中共发现160种不同的基因型,其中,肝型组中p.R778L/p.V1106I基因型的患者发病年龄最晚[(31.0±11.8)岁],脑型组中p.R778L/p.A874V基因型的患者发病年龄最晚[(29.1±13.5)岁]。结论肝型和脑型患者不存在性别比例、发病年龄、铜蓝蛋白水平和角膜K-F阳性率方面的差异;p.R778L、p.P992L和p.A874V是最为常见的ATP7B突变类型,其中p.R778L/p.V1106I和p.R778L/p.A874V基因型的患者呈现更晚的发病年龄。Objective To analyze the clinical phenotype and ATP7B variants characteristics of patients with hepatolenticular degeneration(HLD)from Anhui Province.Methods A retrospectively analysis was performed on Anhui patients(337 cases)diagnosed with HLD in the First Affiliated Hospital of Anhui University of Chinese Medicine from September 2016 to August 2019.Their onset symptoms,onset age,diagnosis age,serum ceruloplasmin level,corneal K-F ring state,and ATP7B variants information were collected.According to the onset characteristics of the patients,they were divided into hepatic type,cerebral type,asymptomatic type,and other types.The differences in clinical characteristics between the hepatic type and the cerebral type patients,as well as the onset age of common genotype patients were compared.Results Among the 337 patients,there were 213 males and 124 females,with an age of onset ranging from 2.0 to 62.6 years[(15.9±9.5)years].Among them,89 cases(26.4%)were hepatic type,171 cases(50.7%)were cerebral type,68 cases(20.2%)were asymptomatic type,and 9 cases(2.7%)were other types.There were no statistically significant differences in gender ratio,onset age,diagnosis age,ceruloplasmin level,and positive state of corneal K-F ring between the hepatic type and the cerebral type patients(all P>0.05).A total of 109 types of ATP7B gene variants were detected,among which the most common were c.2333G>T(p.R778L),c.2975C>T(p.P992L),and c.2621C>T(p.A874V),with allele frequencies of 33.1%,15.7%,and 3.9%,respectively.Among the 296 patients with≥2 ATP7B gene variants detected,a total of 160 different genotypes were found.Among them,the patients with the p.R778L/p.V1106I genotype in the hepatic type group had the latest age of onset[(31.0±11.8)years],and the patients with the p.R778L/p.A874V genotype in the cerebral type group had the latest age of onset[(29.1±13.5)years].Conclusions There are no difference in gender ratio,onset age,diagnosis age,ceruloplasmin level,and positive rate of corneal K-F ring between the hepatic type and

关 键 词：威尔逊病 ATP7B突变 临床特征 安徽省 病例系列研究 

分 类 号：R742.2[医药卫生—神经病学与精神病学]