Espinós Carmen, Ferenci Peter
Unit of Genetics and Genomics of Neuromuscular and Neurodegenerative Disorders, Centro de Investigación Príncipe Felipe (CIPF), Valencia, Spain.
Rare Diseases Joint Units, CIPF-IIS La Fe & INCLIVA, Valencia, Spain.
JHEP Rep. 2020 Apr 18;2(4):100114. doi: 10.1016/j.jhepr.2020.100114. eCollection 2020 Aug.
The diagnosis of Wilson disease is not always easy. For many patients, a combination of tests reflecting disturbed copper metabolism may be needed. Testing for variants has become part of the routine diagnostic approach. The methods of genetic testing include analysis of the 21 coding exons and intronic flanking sequences, in which exons with recurrent variants would be prioritised depending on the mutation frequency in the local population. If sequencing the entire gene cannot identify 2 variants and the suspicion for Wilson disease is high, after reviewing the clinical data, WES (whole-exome sequencing) or WGS (whole-genome sequencing) could be applied. A workflow based on the type and number of variants responsible for Wilson disease is proposed. Genetic testing is indicated for confirmation of diagnosis, family screening, and screening of newborns and infants and in unclear cases suspected of suffering from Wilson disease. However, genetic testing is not a routine screening test for Wilson disease. If no additional variants can be identified, it can be assumed that other hereditary disorders may mimic Wilson disease (congenital disorders of glycosylation, MEDNIK syndrome, idiopathic or primary copper toxicoses).
肝豆状核变性的诊断并非总是容易的。对于许多患者而言，可能需要一系列反映铜代谢紊乱的检查。检测基因变异已成为常规诊断方法的一部分。基因检测方法包括对21个编码外显子和内含子侧翼序列进行分析，其中，根据当地人群中的突变频率，对存在反复出现变异的外显子进行优先排序。如果对整个基因进行测序仍无法鉴定出2个变异，且肝豆状核变性的怀疑度很高，在复查临床资料后，可应用全外显子测序（WES）或全基因组测序（WGS）。本文提出了一种基于导致肝豆状核变性的基因变异类型和数量的工作流程。基因检测用于确诊、家族筛查、新生儿和婴儿筛查以及疑似肝豆状核变性的不明病例。然而，基因检测并非肝豆状核变性的常规筛查试验。如果无法鉴定出其他变异，则可推测其他遗传性疾病可能会模仿肝豆状核变性（先天性糖基化障碍、MEDNIK综合征、特发性或原发性铜中毒）。
