对 53 个中国威尔逊病家系的分子分析：鉴定出 6 个新突变。
Molecular analysis of 53 Chinese families with Wilson's disease: Six novel mutations identified.
机构信息
Department of Medical Genetics, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
Department of Gastroenterology, The Second Xiangya Hospital, Central South University, Changsha, Hunan, 410011, China.
出版信息
Mol Genet Genomic Med. 2021 Sep;9(9):e1735. doi: 10.1002/mgg3.1735. Epub 2021 Jul 29.
BACKGROUND
Wilson's disease (WD) is a rare autosomal recessive inherited disorder that is induced by defects of the ATP7B gene and characterized by damage to the liver and nervous system caused by aberrant copper metabolism. The identification of pathogenic mutations on two homologous chromosomes has become the gold standard for the diagnosis of WD.
METHODS
Sanger sequencing and multiplex ligation-dependent probe amplification (MLPA) were combined to establish a genetic diagnosis for patients from 53 unrelated Chinese WD families.
RESULTS
Biallelic mutations were detected by Sanger sequencing in 50 of the probands, while single heterozygous mutations were detected in the remaining three probands. A total of 45 diverse pathogenic mutations were detected, and 6 previously unreported mutations were involved. Five asymptomatic patients were screened from 85 family members of 38 probands participating in the study.
CONCLUSION
This study contributes to the enlargement of the mutational spectrum of the ATP7B gene among the population of China and highlights the significance of genetic testing for asymptomatic patients.
背景
威尔逊病（WD）是一种罕见的常染色体隐性遗传性疾病，由 ATP7B 基因突变引起，其特征是铜代谢异常导致肝和神经系统损伤。两条同源染色体上的致病性突变的鉴定已成为 WD 诊断的金标准。
方法
采用 Sanger 测序和多重连接依赖性探针扩增（MLPA）相结合的方法，对 53 个无关中国 WD 家系的患者进行遗传诊断。
结果
通过 Sanger 测序在 50 名先证者中检测到双等位基因突变，而在其余 3 名先证者中检测到单杂合突变。共检测到 45 种不同的致病性突变，其中涉及 6 种以前未报道过的突变。在 38 名先证者的 85 名家庭成员中，筛查出 5 名无症状患者。
结论
本研究丰富了中国人群 ATP7B 基因突变谱，强调了对无症状患者进行基因检测的重要性。
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