中国 Wilson 病中 ATP7B 基因 R778L 突变的系统评价和荟萃分析。

A Systematic Review and Meta-Analysis of the R778L Mutation in ATP7B With Wilson Disease in China.

机构信息

Department of Neurology at The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, Zhejiang, China.

The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, National Regional Medical Center for Children, Hangzhou, Zhejiang, China.

出版信息

Pediatr Neurol. 2023 Aug;145:135-147. doi: 10.1016/j.pediatrneurol.2023.04.026. Epub 2023 May 8.

DOI:10.1016/j.pediatrneurol.2023.04.026

PMID:37354629

Abstract

BACKGROUND

Wilson disease (WD) is a hereditary disorder of copper metabolism, caused by mutations in the ATP7B gene. There are more than 1000 pathogenic variants identified in ATP7B. R778L is the most common ATP7B mutation in China.

METHODS

To estimate whether R778L is associated with the onset age of WD and other clinical variables. Genotyping results of ATP7B gene were collected in our 22 patients with WD. We then conducted a systematic review and meta-analysis in databases, using the keywords Wilson disease and R778L mutation.

RESULTS

After the screening, a total of 23 studies were included, including 3007 patients with WD. Patients with R778L mutation presented at an earlier age (standardized mean difference [SMD] = -0.18 [95% confidence interval, -0.28 to 0.08], P = 0.0004) and had lower ceruloplasmin concentration (SMD = -0.21 [95% confidence interval, -0.40 to -0.02], P = 0.03) than the patients without the R778L mutation. However, sex (odds ratio [OR] = 1.07 [95% confidence interval, 0.89 to 1.29], P = 0.32) and first presentation were not associated with R778L mutation in WD (hepatic: OR = 1.37 [95% confidence interval, 0.87 to 2.16, P = 0.17; neurological: OR = 0.79 [95% confidence interval, 0.48 to 1.30, P = 0.35; mix: OR = 1.04 [95% confidence interval, 0.42 to 2.53, P = 0.87; asymptomatic/others: OR = 1.98 [95% confidence interval, 0.49 to 7.96, P = 0.34).

CONCLUSIONS

Our results indicated that the R778L mutation is associated with an earlier presentation and lower ceruloplasmin concentration in China.

摘要

背景

威尔逊病（WD）是一种铜代谢遗传性疾病，由 ATP7B 基因突变引起。在 ATP7B 中已鉴定出超过 1000 种致病性变异。R778L 是中国最常见的 ATP7B 突变。

方法

评估 R778L 是否与 WD 的发病年龄和其他临床变量相关。收集了我们 22 例 WD 患者的 ATP7B 基因的基因分型结果。然后，我们使用关键字“Wilson 病”和“R778L 突变”在数据库中进行了系统评价和荟萃分析。

结果

经过筛选，共纳入 23 项研究，包括 3007 例 WD 患者。携带 R778L 突变的患者发病年龄较早（标准化均数差 [SMD] = -0.18 [95%置信区间，-0.28 至 0.08]，P = 0.0004），且铜蓝蛋白浓度较低（SMD = -0.21 [95%置信区间，-0.40 至 -0.02]，P = 0.03）。然而，WD 中性别（比值比 [OR] = 1.07 [95%置信区间，0.89 至 1.29]，P = 0.32）和首发表现与 R778L 突变无关（肝型：OR = 1.37 [95%置信区间，0.87 至 2.16，P = 0.17；神经型：OR = 0.79 [95%置信区间，0.48 至 1.30，P = 0.35；混合型：OR = 1.04 [95%置信区间，0.42 至 2.53，P = 0.87；无症状/其他型：OR = 1.98 [95%置信区间，0.49 至 7.96，P = 0.34）。