Wilson’s Disease—Genetic Puzzles with Diagnostic Implications
(1) Introduction: Wilson’s disease (WND) is an autosomal recessive disorder of copper metabolism. The WND gene is <i>ATP7B</i>, located on chromosome 13. WND is characterized by high clinical variability, which causes diagnostic difficulties. (2) Methods: The PubMed, Science Direct, and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-03-01
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| Series: | Diagnostics |
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| Online Access: | https://www.mdpi.com/2075-4418/13/7/1287 |
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| author | Grażyna Gromadzka Maria Bendykowska Adam Przybyłkowski |
| author_facet | Grażyna Gromadzka Maria Bendykowska Adam Przybyłkowski |
| author_sort | Grażyna Gromadzka |
| collection | DOAJ |
| description | (1) Introduction: Wilson’s disease (WND) is an autosomal recessive disorder of copper metabolism. The WND gene is <i>ATP7B</i>, located on chromosome 13. WND is characterized by high clinical variability, which causes diagnostic difficulties. (2) Methods: The PubMed, Science Direct, and Wiley Online Library medical databases were reviewed using the following phrases: “Wilson’s disease”, “ATP7B genotype”, “genotype-phenotype”, “epigenetics”, “genetic modifiers”, and their combinations. Publications presenting the results of experimental and clinical studies, as well as review papers, were selected, which concerned: (i) the diversity of genetic strategies and tests used in WND diagnosis; (ii) the difficulties of genetic diagnosis, including uncertainty as to the pathogenicity of variants; (iii) genetic counseling; (iv) phenotypic effects of <i>ATP7B</i> variants in patients with WND and in heterozygous carriers (HzcWND); (v) genetic and epigenetics factors modifying the clinical picture of the disease. (3) Results and conclusions: The genetic diagnosis of WND is carried out using a variety of strategies and tests. Due to the large number of known variants in the <i>ATP7B</i> gene (>900), the usefulness of genetic tests in routine diagnostics is still relatively small and even analyses performed using the most advanced technologies, including next-generation sequencing, require additional tests, including biochemical evidence of abnormal copper metabolism, to confirm the diagnosis of WND. Pseudodominant inheritance, the presence of three various pathogenic variants in the same patient, genotypes indicating the possibility of segmental uniparental disomy, have been reported. Genotype–phenotype relationships in WND are complex. The <i>ATP7B</i> genotype, to some extent, determines the clinical picture of the disease, but other genetic and epigenetic modifiers are also relevant. |
| first_indexed | 2024-03-11T05:39:39Z |
| format | Article |
| id | doaj.art-3dbbcefb88e84414ba52d8f506469d64 |
| institution | Directory Open Access Journal |
| issn | 2075-4418 |
| language | English |
| last_indexed | 2024-03-11T05:39:39Z |
| publishDate | 2023-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Diagnostics |
| spelling | doaj.art-3dbbcefb88e84414ba52d8f506469d642023-11-17T16:30:28ZengMDPI AGDiagnostics2075-44182023-03-01137128710.3390/diagnostics13071287Wilson’s Disease—Genetic Puzzles with Diagnostic ImplicationsGrażyna Gromadzka0Maria Bendykowska1Adam Przybyłkowski2Medical Faculty, Collegium Medicum, Cardinal Stefan Wyszyński University in Warsaw, ul. Wóycickiego 1/3, 01-938 Warsaw, PolandMedical Faculty, Collegium Medicum, Cardinal Stefan Wyszyński University in Warsaw, ul. Wóycickiego 1/3, 01-938 Warsaw, PolandDepartment of Gastroenterology and Internal Medicine, Medical University of Warsaw, 02-091 Warszawa, Poland(1) Introduction: Wilson’s disease (WND) is an autosomal recessive disorder of copper metabolism. The WND gene is <i>ATP7B</i>, located on chromosome 13. WND is characterized by high clinical variability, which causes diagnostic difficulties. (2) Methods: The PubMed, Science Direct, and Wiley Online Library medical databases were reviewed using the following phrases: “Wilson’s disease”, “ATP7B genotype”, “genotype-phenotype”, “epigenetics”, “genetic modifiers”, and their combinations. Publications presenting the results of experimental and clinical studies, as well as review papers, were selected, which concerned: (i) the diversity of genetic strategies and tests used in WND diagnosis; (ii) the difficulties of genetic diagnosis, including uncertainty as to the pathogenicity of variants; (iii) genetic counseling; (iv) phenotypic effects of <i>ATP7B</i> variants in patients with WND and in heterozygous carriers (HzcWND); (v) genetic and epigenetics factors modifying the clinical picture of the disease. (3) Results and conclusions: The genetic diagnosis of WND is carried out using a variety of strategies and tests. Due to the large number of known variants in the <i>ATP7B</i> gene (>900), the usefulness of genetic tests in routine diagnostics is still relatively small and even analyses performed using the most advanced technologies, including next-generation sequencing, require additional tests, including biochemical evidence of abnormal copper metabolism, to confirm the diagnosis of WND. Pseudodominant inheritance, the presence of three various pathogenic variants in the same patient, genotypes indicating the possibility of segmental uniparental disomy, have been reported. Genotype–phenotype relationships in WND are complex. The <i>ATP7B</i> genotype, to some extent, determines the clinical picture of the disease, but other genetic and epigenetic modifiers are also relevant.https://www.mdpi.com/2075-4418/13/7/1287Wilson’s diseasediagnosticscoppergeneticsepigeneticsgenotype |
| spellingShingle | Grażyna Gromadzka Maria Bendykowska Adam Przybyłkowski Wilson’s Disease—Genetic Puzzles with Diagnostic Implications Diagnostics Wilson’s disease diagnostics copper genetics epigenetics genotype |
| title | Wilson’s Disease—Genetic Puzzles with Diagnostic Implications |
| title_full | Wilson’s Disease—Genetic Puzzles with Diagnostic Implications |
| title_fullStr | Wilson’s Disease—Genetic Puzzles with Diagnostic Implications |
| title_full_unstemmed | Wilson’s Disease—Genetic Puzzles with Diagnostic Implications |
| title_short | Wilson’s Disease—Genetic Puzzles with Diagnostic Implications |
| title_sort | wilson s disease genetic puzzles with diagnostic implications |
| topic | Wilson’s disease diagnostics copper genetics epigenetics genotype |
| url | https://www.mdpi.com/2075-4418/13/7/1287 |
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