| Autor: |
Marlene Panzer, André Viveiros, Benedikt Schaefer, Nadja Baumgartner, Klaus Seppi, Atbin Djamshidian, Theodor Todorov, William J. H. Griffiths, Eckart Schott, Markus Schuelke, Dennis Eurich, Albert Friedrich Stättermayer, Adrian Bomford, Pierre Foskett, Julia Vodopiutz, Rudolf Stauber, Elke Pertler, Bernhard Morell, Herbert Tilg, Thomas Müller, Stefan Kiechl, Raul Jimenez‐Heredia, Karl Heinz Weiss, Si Houn Hahn, Andreas Janecke, Peter Ferenci, Heinz Zoller |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Zdroj: |
Hepatology Communications, Vol 6, Iss 7, Pp 1611-1619 (2022) |
| Druh dokumentu: |
article |
| ISSN: |
2471-254X |
| DOI: |
10.1002/hep4.1922 |
| Popis: |
Abstract Wilson disease (WD) is caused by biallelic pathogenic variants in adenosine triphosphatase copper‐transporting beta (ATP7B); however, genetic testing identifies only one or no pathogenic ATP7B variant in a number of patients with WD. Synonymous single‐nucleotide sequence variants have been recognized as pathogenic in individual families. The aim of the present study was to evaluate the prevalence and disease mechanism of the synonymous variant c.2292C>T (p.Phe764=) in WD. A cohort of 280 patients with WD heterozygous for a single ATP7B variant was investigated for the presence of c.2292C>T (p.Phe764=). In this cohort of otherwise genetically unexplained WD, the allele frequency of c.2292C>T (p.Phe764=) was 2.5% (14 of 560) compared to 7.1 × 10−6 in the general population (2 of 280,964 in the Genome Aggregation Database; p < 10−5; Fisher exact test). In an independent United Kingdom (UK) cohort, 2 patients with WD homozygous for p.Phe764= were identified. RNA analysis of ATP7B transcripts from patients homozygous or heterozygous for c.2292C>T and control fibroblasts showed that this variant caused high expression of an ATP7B transcript variant lacking exon 8. Conclusion: The synonymous ATP7B variant c.2292C>T (p.Phe764=) causes abnormal messenger RNA processing of ATP7B transcripts and is associated with WD in compound heterozygotes and homozygotes. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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