Ljubić Hana, Kalauz Mirjana, Telarović Srđana, Ferenci Peter, Ostojić Rajko, Noli Maria Cristina, Lepori Maria Barbara, Hrstić Irena, Vuković Jurica, Premužić Marina, Radić Davor, Ravić Katja Grubelić, Sertić Jadranka, Merkler Ana, Barišić Ana Acman, Loudianos Georgios, Vucelić Boris
1 Department of Laboratory Diagnostics, University Hospital Centre Zagreb , Zagreb, Croatia .
2 Department of Internal Medicine, University Hospital Centre Zagreb , Zagreb, Croatia .
Genet Test Mol Biomarkers. 2016 Mar;20(3):112-7. doi: 10.1089/gtmb.2015.0213. Epub 2016 Jan 22.
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism, characterized by its accumulation in tissues which results in hepatic, neurological, and/or psychiatric symptoms. The aim of this study was to investigate the genetics of WD in Croatian patients.
Correlation of the clinical presentation subtype and the age at onset of the diagnosis of WD with the ATP7B genotype was investigated in a group of Croatian WD patients. DNA from peripheral blood samples was tested for the p.His1069Gln by direct mutational analysis and other polymorphisms were identified by sequence analysis of coding and flanking intronic regions of ATP7B gene.
In the group of 75 WD patients of Croatian origin, 18 different mutations in ATP7B gene were detected, three of which were novel. The p.His1069Gln mutation was most frequent, being detected in 44 Croatian WD patients (58.7%). Most ATP7B mutations (90.4%) were located in exons 5, 8, 13, 14, and 15.
Clinical diagnosis of WD was confirmed in 59 patients by detecting mutations on both ATP7B alleles. The age at onset of WD and the type of WD clinical presentation showed no significant correlation with the ATP7B genotype.
威尔逊病（WD）是一种常染色体隐性铜代谢紊乱疾病，其特征是铜在组织中蓄积，从而导致肝脏、神经和/或精神症状。本研究的目的是调查克罗地亚患者中WD的遗传学情况。
在一组克罗地亚WD患者中，研究WD临床表现亚型和诊断时的发病年龄与ATP7B基因型之间的相关性。通过直接突变分析检测外周血样本DNA中的p.His1069Gln，并通过对ATP7B基因编码区和侧翼内含子区域进行序列分析来鉴定其他多态性。
在75名克罗地亚裔WD患者组中，检测到ATP7B基因有18种不同突变，其中3种为新发现的突变。p.His1069Gln突变最为常见，在44名克罗地亚WD患者（58.7%）中检测到。大多数ATP7B突变（90.4%）位于外显子5、8、13、14和15中。
通过检测两个ATP7B等位基因上的突变，59名患者的WD临床诊断得到证实。WD的发病年龄和WD临床表现类型与ATP7B基因型无显著相关性。
