Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice?

6533b861fe1ef96bd12c43ec

RESEARCH PRODUCT

Are the new genetic tools for diagnosis of Wilson disease helpful in clinical practice?

subject

Disease Review Indian childhood cirrhosis Bioinformatics DNA sequencing WES whole-exome sequencing PFIC progressive familial intrahepatic cholestasis Internal Medicine medicine Immunology and Allergy Multiplex ligation-dependent probe amplification WGS whole-genome sequencing Exome sequencing Genetic testing Wilson disease Whole genome sequencing Whole-genome sequencing Hepatology medicine.diagnostic_test MEDNIK syndrome business.industry Copper metabolism Gastroenterology MLPA multiplex ligation-dependent probe amplification medicine.disease ICC Indian childhood cirrhosis NGS next-generation sequencing DMR differentially methylated regions Whole-exome sequencing Next-generation sequencing business ICT idiopathic or primary copper toxicosis CDG congenital disorders of glycosylation Genetic diseases

description

Summary 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 ATP7B 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 ATP7B 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 ATP7B 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).

year	journal	country	edition	language
2020-04-01	JHEP Reports

10.1016/j.jhepr.2020.100114 http://europepmc.org/articles/PMC7322184