Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia
Wilson’s disease (WD) is a copper metabolism disorder, caused by allelic variants in the ATP7B gene. Wilson’s disease can be diagnosed by clinical symptoms, increased copper and decreased cerulopasmin levels, which could all also be by other genetic variants beyond the ATP7B gene, e.g., disturbed ce...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Sciendo
2019-12-01
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| Series: | Balkan Journal of Medical Genetics |
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| Online Access: | https://doi.org/10.2478/bjmg-2019-0023 |
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| author | Zarina A Tolmane I Krumina Z Tutane AI Gailite L |
| author_facet | Zarina A Tolmane I Krumina Z Tutane AI Gailite L |
| author_sort | Zarina A |
| collection | DOAJ |
| description | Wilson’s disease (WD) is a copper metabolism disorder, caused by allelic variants in the ATP7B gene. Wilson’s disease can be diagnosed by clinical symptoms, increased copper and decreased cerulopasmin levels, which could all also be by other genetic variants beyond the ATP7B gene, e.g., disturbed ceruloplasmin biosynthesis can be caused by pathogenic allelic variants of the CP gene. Copper metabolism in the organism is affected by several molecules, but pathogenic variants and related phenotypes are described with COMMD1 and ATOX1 genes. The aim of the study was to test other genes, CP, ATOX1 and COMMD1, for possible influence to the manifestation of WD. Patients were enrolled on the basis of Leipzig’s diagnostic criteria, 64 unrelated patients with confirmed WD. Direct sequencing of promoter region of the CP gene and ATOX1 and COMMD1 gene exons was conducted. Statistically significant differences were found between the two variants in the CP gene and the ATP7B genotype (rs66508328 variant AA genotype and the rs11708215 variant GG genotype) were more common in WD patients with an unconfirmed ATP7B genotype. One allelic (intronic) variant was found in the ATOX1 gene without causing the functional changes of the gene. Three allelic variants were identified in the COMMD1 gene. No statistically significant differences were found between allele and genotype frequencies and the first clinical manifestations of WD. Different variants of the CP gene contributed to a WD-like phenotype in clinically confirmed WD patients with neurological symptoms and without identified pathogenic variants in the ATP7B gene. Allelic variants in the ATOX1 and COMMD1 genes do not modify the clinical manifestation of WD in Latvian patients. (266 words) |
| first_indexed | 2024-03-12T19:10:29Z |
| format | Article |
| id | doaj.art-c9ca5e851b8846eeb71b30eee0201d65 |
| institution | Directory Open Access Journal |
| issn | 1311-0160 |
| language | English |
| last_indexed | 2024-03-12T19:10:29Z |
| publishDate | 2019-12-01 |
| publisher | Sciendo |
| record_format | Article |
| series | Balkan Journal of Medical Genetics |
| spelling | doaj.art-c9ca5e851b8846eeb71b30eee0201d652023-08-02T05:57:34ZengSciendoBalkan Journal of Medical Genetics1311-01602019-12-01222374210.2478/bjmg-2019-0023bjmg-2019-0023Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in LatviaZarina A0Tolmane I1Krumina Z2Tutane AI3Gailite L4Scientific Laboratory of Molecular Genetics, Rīga Stradiņš University, Riga, LatviaRiga East Clinical University Hospital, stationary “Latvian Centre of Infectious Diseases”, Riga, LatviaDepartment of Biology and Microbiology, Rīga Stradiņš University, Riga, LatviaScientific Laboratory of Molecular Genetics, Rīga Stradiņš University, Riga, LatviaScientific Laboratory of Molecular Genetics, Rīga Stradiņš University, Riga, LatviaWilson’s disease (WD) is a copper metabolism disorder, caused by allelic variants in the ATP7B gene. Wilson’s disease can be diagnosed by clinical symptoms, increased copper and decreased cerulopasmin levels, which could all also be by other genetic variants beyond the ATP7B gene, e.g., disturbed ceruloplasmin biosynthesis can be caused by pathogenic allelic variants of the CP gene. Copper metabolism in the organism is affected by several molecules, but pathogenic variants and related phenotypes are described with COMMD1 and ATOX1 genes. The aim of the study was to test other genes, CP, ATOX1 and COMMD1, for possible influence to the manifestation of WD. Patients were enrolled on the basis of Leipzig’s diagnostic criteria, 64 unrelated patients with confirmed WD. Direct sequencing of promoter region of the CP gene and ATOX1 and COMMD1 gene exons was conducted. Statistically significant differences were found between the two variants in the CP gene and the ATP7B genotype (rs66508328 variant AA genotype and the rs11708215 variant GG genotype) were more common in WD patients with an unconfirmed ATP7B genotype. One allelic (intronic) variant was found in the ATOX1 gene without causing the functional changes of the gene. Three allelic variants were identified in the COMMD1 gene. No statistically significant differences were found between allele and genotype frequencies and the first clinical manifestations of WD. Different variants of the CP gene contributed to a WD-like phenotype in clinically confirmed WD patients with neurological symptoms and without identified pathogenic variants in the ATP7B gene. Allelic variants in the ATOX1 and COMMD1 genes do not modify the clinical manifestation of WD in Latvian patients. (266 words)https://doi.org/10.2478/bjmg-2019-0023copper metabolismdecreased blood ceruloplasminwilson’s disease (wd) |
| spellingShingle | Zarina A Tolmane I Krumina Z Tutane AI Gailite L Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia Balkan Journal of Medical Genetics copper metabolism decreased blood ceruloplasmin wilson’s disease (wd) |
| title | Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia |
| title_full | Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia |
| title_fullStr | Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia |
| title_full_unstemmed | Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia |
| title_short | Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia |
| title_sort | association of variants in the cp atox1 and commd1 genes with wilson disease symptoms in latvia |
| topic | copper metabolism decreased blood ceruloplasmin wilson’s disease (wd) |
| url | https://doi.org/10.2478/bjmg-2019-0023 |
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