Hana Ljubić1, Mirjana Kalauz2, Srđana Telarović3, Peter Ferenci4, Rajko Ostojić2, Maria Cristina Noli5, Maria Barbara Lepori5, Irena Hrstić6, Jurica Vuković7, Marina Premužić2, Davor Radić2, Katja Grubelić Ravić2, Jadranka Sertić1, Ana Merkler1, Ana Acman Barišić1, Georgios Loudianos8, Boris Vucelić2. 1. 1 Department of Laboratory Diagnostics, University Hospital Centre Zagreb , Zagreb, Croatia . 2. 2 Department of Internal Medicine, University Hospital Centre Zagreb , Zagreb, Croatia . 3. 3 Department of Neurology, University Hospital Centre Zagreb , Zagreb, Croatia . 4. 4 Division of Gastroenterology and Hepatology, Department of Internal Medicine III, Medical University of Vienna , Vienna, Austria . 5. 5 Department of Public Health and Clinical and Molecular Medicine, University of Cagliari , Cagliari, Italy . 6. 6 Department of Internal Medicine, General Hospital Pula , Pula, Croatia . 7. 7 Department of Pediatrics, University Hospital Centre Zagreb , Zagreb, Croatia . 8. 8 Ospedale Regionale Microcitemie , ASL 8, Cagliari, Italy .
Abstract
AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
AIMS: 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. METHODS: 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 WDpatients. 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. RESULTS: In the group of 75 WDpatients 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 WDpatients (58.7%). Most ATP7B mutations (90.4%) were located in exons 5, 8, 13, 14, and 15. CONCLUSIONS: 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.
Authors: Nguyen Thi Mai Huong; Nguyen Thi Kim Lien; Ngo Diem Ngoc; Nguyen Thi Phuong Mai; Nguyen Pham Anh Hoa; Le Thanh Hai; Phan Van Chi; Ta Thanh Van; Tran Van Khanh; Nguyen Huy Hoang Journal: BMC Med Genet Date: 2018-06-18 Impact factor: 2.103