Review
Cell Biology
Som Dev, Robert L. Kruse, James P. Hamilton, Svetlana Lutsenko
Summary: This review summarizes recent advances in the characterization of Wilson disease pathophysiology and discusses emerging targets for improving diagnosis and treatment.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Medical Laboratory Technology
Siyu Jia, Xiaojin Li, Wei Zhang, Bei Zhang, Zhen Wu, Weijia Duan, Xiaojuan Ou, Donghu Zhou, Jian Huang
Summary: In this study, a reliable microarray system was established for the rapid detection of 24 ATP7B mutations in Chinese patients with Wilson disease. The microarray showed high sensitivity and specificity, making it a suitable method for genetic diagnosis of Wilson disease in China.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Medical Laboratory Technology
Chenjun Huang, Meng Fang, Xiao Xiao, Zhiyuan Gao, Ying Wang, Chunfang Gao
Summary: This study revealed the genetic defects of Chinese families and individuals with Wilson disease, enriching the worldwide mutation spectrum of the ATP7B gene and providing valuable information for studying ATP7B mutation types in the Chinese population.
JOURNAL OF CLINICAL LABORATORY ANALYSIS
(2022)
Article
Gastroenterology & Hepatology
Christopher J. Collins, Fan Yi, Remwilyn Dayuha, Phi Duong, Simon Horslen, Michelle Camarata, Ayse K. Coskun, Roderick H. J. Houwen, Tudor L. Pop, Heinz Zoller, Han-Wook Yoo, Sung Won Jung, Karl H. Weiss, Michael L. Schilsky, Peter Ferenci, Si Houn Hahn
Summary: Quantification of ATP7B peptide effectively identified Wilson disease patients in 92.1% of presented cases, reducing ambiguities from ceruloplasmin and genetic analysis. It provides clarity to patients with ambiguous genetic results, aiding significantly in noninvasive diagnosis. A proposed diagnostic score and algorithm incorporating ATP7B peptide concentrations can be a rapid supplement to current Leipzig scoring systems.
Article
Biochemistry & Molecular Biology
Donghu Zhou, Siyu Jia, Liping Yi, Zhen Wu, Yi Song, Bei Zhang, Yanmeng Li, Xiaoxi Yang, Anjian Xu, Xiaojin Li, Wei Zhang, Weijia Duan, Zhenkun Li, Saiping Qi, Zhibin Chen, Qin Ouyang, Jidong Jia, Jian Huang, Xiaojuan Ou, Hong You
Summary: This study identified disease-causing variants in potential modifier genes associated with Wilson disease through whole-exome sequencing and isobaric tags for relative and absolute quantitation (iTRAQ) approaches. One of the modifier genes showed a significantly higher mutation frequency in Wilson disease patients compared to healthy donors.
Review
Biochemistry & Molecular Biology
Bryce Blades, Scott Ayton, Ya Hui Hung, Ashley Bush, Sharon La Fontaine
Summary: The complex and inverse relationship between copper and lipid metabolism has implications for diseases involving dyslipidemia. Understanding these pathways may provide druggable targets for therapeutic intervention. Tissue-specific roles of the copper regulatory protein ATP7B further elucidate the association between copper and lipid metabolism.
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
(2021)
Review
Medicine, General & Internal
Ana Lucena-Valera, Pilar Ruz-Zafra, Javier Ampuero
Summary: Wilson's disease is a rare hereditary disorder caused by a deficiency in the ATP7B transporter. It results in copper accumulation primarily in the liver, and secondarily in other organs such as the central nervous system. The disease has a wide spectrum of symptoms, ranging from asymptomatic to acute liver failure. Diagnosis requires a combination of clinical signs, symptoms, and diagnostic tests. Treatment involves lifelong maintenance with chelating agents and copper absorption inhibitors, and liver transplant may be an option for end-stage liver disease patients.
Article
Genetics & Heredity
Zhongyan Xiao, Yuan Yang, Hui Huang, Haiyan Tang, Liqun Liu, Jianguang Tang, Xiaoliu Shi
Summary: The study successfully established a genetic diagnosis for patients from 53 unrelated Chinese WD families using a combination of Sanger sequencing and MLPA, identifying 45 diverse pathogenic mutations with 6 of them being previously unreported. The significance of genetic testing for asymptomatic patients was highlighted, with five asymptomatic patients identified from the study.
MOLECULAR GENETICS & GENOMIC MEDICINE
(2021)
Article
Genetics & Heredity
Guo-Min Yang, Rou-Min Wang, Nan Xia, Zi-Wei Zheng, Yi Dong, Zhi-Ying Wu
Summary: This study revealed a regional-specific distribution feature for p.T935M in mainland Chinese population. Linkage disequilibrium was shown at the three markers for all three variants, with common haplotypes specific for p.R778L, p.P992L, and p.T935M identified. These common haplotypes indicate a founder effect contributing to the emergence of the three prevalent pathogenic variants observed in Wilson's disease, expanding our understanding of genetic diversity across regions.
Review
Biochemistry & Molecular Biology
Ana Sanchez-Monteagudo, Edna Ripolles, Marina Berenguer, Carmen Espinos
Summary: Wilson disease is a rare disorder with a variable clinical presentation, requiring early diagnosis for effective treatment. The clinical diagnosis is based on the Leipzig score, but some patients may have conditions resembling WD, leading to uncertainty. Current biomarkers like ceruloplasmin and copper levels are not sufficient, highlighting the need for better markers to improve diagnosis and prognosis.
Article
Gastroenterology & Hepatology
Saleh A. Alqahtani, Rose Chami, Dua Abuquteish, Shannon M. Vandriel, Charesse Yap, Liyana Kukkadi, Aishwarya Parmar, Amrita Mundh, Eve A. Roberts, Binita M. Kamath, Iram Siddiqui
Summary: This study compared the histological features of Wilson disease (WD) in children with non-alcoholic fatty liver disease (NAFLD) and autoimmune hepatitis (AIH). It found that there was considerable overlap in the light microscopic findings, but ultrastructural findings of mitochondrial abnormalities were important in distinguishing WD from NAFLD and AIH.
LIVER INTERNATIONAL
(2022)
Article
Medicine, General & Internal
Cigdem Yuce Kahraman, Ali Islek, Abdulgani Tatar, Ozlem Ozdemir, Adil Mardinglu, Hasan Turkez
Summary: Wilson disease is a rare autosomal recessive inherited disorder characterized by excess copper storage in different tissues. The clinical presentations are highly varied, primarily involving hepatic and neurological conditions. Early diagnosis and genetic analysis play crucial roles in treatment and family risk screening.
MEDICINA-LITHUANIA
(2021)
Article
Multidisciplinary Sciences
Abigael Muchenditsi, C. Conover Talbot, Aline Gottlieb, Haojun Yang, Byunghak Kang, Tatiana Boronina, Robert Cole, Li Wang, Som Dev, James P. Hamilton, Svetlana Lutsenko
Summary: The study found that global inactivation of Atp7b enhances and specifically modifies the hepatocyte response to copper overload, while the loss of Atp7b only in hepatocytes causes dysregulation of lipid and nucleic acid metabolism.
SCIENTIFIC REPORTS
(2021)
Article
Pediatrics
Aabha Nagral, Snehal Mallakmir, Nikita Garg, Kritika Tiwari, Suzena Masih, Nishtha Nagral, Ojas Unavane, Ajay Jhaveri, Shubha Phadke, GaneshPrasad ArunKumar, Rakesh Aggarwal
Summary: This study reports genotype data of Wilson disease patients from India, adding to the available spectrum of causative variants in ATP7B gene. It also found genetic and phenotypic diversity in the Indian population.
INDIAN JOURNAL OF PEDIATRICS
(2023)
Article
Gastroenterology & Hepatology
Mingming Li, Jing Ma, Wenlong Wang, Xu Yang, Kaizhong Luo
Summary: In this study, three novel mutations were identified in 103 WD patients from southern China, enriching the mutational spectrum of the ATP7B gene. The most common mutations were c.2333G>T (p.Arg778 Leu) and c.2975C>T (p.Pro992Leu), with allelic frequencies of 28.6% and 13.0%, respectively. Phenotype-genotype correlation analysis revealed significant associations between certain mutations and clinical characteristics of WD, providing insights into the population genetics of WD in China.
BMC GASTROENTEROLOGY
(2021)