<abstract xmlns="http://www.w3.org/1999/xhtml">

<p>Wilson’s disease (WD) is a copper metabolism disorder, caused by allelic variants in the <italic>ATP7B</italic> 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 <italic>ATP7B</italic> gene, <italic>e.g</italic>., disturbed ceruloplasmin biosynthesis can be caused by pathogenic allelic variants of the <italic>CP</italic> gene. Copper metabolism in the organism is affected by several molecules, but pathogenic variants and related phenotypes are described with <italic>COMMD1</italic> and <italic>ATOX1</italic> genes. The aim of the study was to test other genes, <italic>CP</italic>, <italic>ATOX1</italic> and <italic>COMMD1</italic>, 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 <italic>CP</italic> gene and <italic>ATOX1</italic> and <italic>COMMD1</italic> gene exons was conducted. Statistically significant differences were found between the two variants in the <italic>CP</italic> gene and the <italic>ATP7B</italic> genotype (rs66508328 variant AA genotype and the rs11708215 variant GG genotype) were more common in WD patients with an unconfirmed <italic>ATP7B</italic> genotype. One allelic (intronic) variant was found in the <italic>ATOX1</italic> gene without causing the functional changes of the gene. Three allelic variants were identified in the <italic>COMMD1</italic> gene. No statistically significant differences were found between allele and genotype frequencies and the first clinical manifestations of WD. Different variants of the <italic>CP</italic> gene contributed to a WD-like phenotype in clinically confirmed WD patients with neurological symptoms and without identified pathogenic variants in the <italic>ATP7B</italic> gene. Allelic variants in the <italic>ATOX1</italic> and <italic>COMMD1</italic> genes do not modify the clinical manifestation of WD in Latvian patients. (266 words)</p></abstract>

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)

Association of variants in the <italic>CP</italic>, <italic>ATOX1</italic> and <italic>COMMD1</italic> genes with Wilson disease symptoms in Latvia

Balkan Journal of Medical Genetics

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Association of variants in the ,  and  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,...

Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia

Article Category: Original Article

Publicado en línea: 21 dic 2019

Páginas: 37 - 42

DOI: https://doi.org/10.2478/bjmg-2019-0023

Palabras clave
Copper metabolism, Decreased blood ceruloplasmin, Wilson’s disease (WD)

© 2019 Zarina A, Tolmane I, Krumina Z, Tutane AI, Gailite L, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Association of variants in the CP, ATOX1 and COMMD1 genes with Wilson disease symptoms in Latvia

Article Category: Original Article

Publicado en línea: 21 dic 2019

Páginas: 37 - 42

DOI: https://doi.org/10.2478/bjmg-2019-0023

Palabras claveCopper metabolism, Decreased blood ceruloplasmin, Wilson’s disease (WD)

© 2019 Zarina A, Tolmane I, Krumina Z, Tutane AI, Gailite L, published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Palabras clave
Copper metabolism, Decreased blood ceruloplasmin, Wilson’s disease (WD)