Spectrum of Pathogenic Variants of the ATP7B Gene and Genotype–Phenotype Correlation in Eastern Eurasian Patient Cohorts with Wilson’s Disease
<b>Background/Objectives:</b> Wilson’s disease (WD) (OMIM 277900) or hepatolenticular degeneration is an autosomal recessive disorder caused by impaired copper excretion with subsequent accumulation in the liver, brain, and other tissues of the body. The defects in copper metabolism are...
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2024-12-01
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| author | Mikhail Garbuz Elena Ovchinnikova Anna Ovchinnikova Valeriya Vinokurova Yulya Aristarkhova Olga Kuziakova Mariya Mashurova Vadim Kumeiko |
| author_facet | Mikhail Garbuz Elena Ovchinnikova Anna Ovchinnikova Valeriya Vinokurova Yulya Aristarkhova Olga Kuziakova Mariya Mashurova Vadim Kumeiko |
| author_sort | Mikhail Garbuz |
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| description | <b>Background/Objectives:</b> Wilson’s disease (WD) (OMIM 277900) or hepatolenticular degeneration is an autosomal recessive disorder caused by impaired copper excretion with subsequent accumulation in the liver, brain, and other tissues of the body. The defects in copper metabolism are based on various pathogenic variants of the ATP7B gene encoding copper-transporting P-type ATPase. The aim of this work is to search for pathogenic variants of the ATP7B gene among Eastern Eurasian patient cohorts and to pick correlations between pathogenic variants, gender, age of onset of the disease, and the course of the disease. <b>Methods</b>: The material for the study was the biomaterial of 100 people. The search for mutations was carried out by Sanger sequencing. Multiple alignment of nucleotide sequences and their analysis was performed using the MEGA-X software. To study the genotype-phenotypic correlation, an analysis of the medical records of each patient was carried out. <b>Results</b>: Most common pathogenic variant (48%) in the sample is p.His1069Gln (c.3207C>A), located in exon 14 of the ATP7B gene. Pathogenic variants of p.Glu1064Lys (c.3190G>A)—20%—and p.Met769HisfsTer26 (c.2304insC)—8%—of exons 14 and 8 were also common. For patients with pathogenic alleles p.His1069Gln (c.3207C>A) and p.Glu1064Lys (c.3190G>A), typical deviations are mental and neurological manifestations of WD. In patients with the pathogenic allele p.Met769HisfsTer26 (c.2304insC), deviations are more characteristic of the liver and a combination of various symptoms that are atypical for WD. <b>Conclusions</b>: In this study, we were able to obtain differences in symptoms in patients with different pathogenic alleles of the ATP7B gene. |
| format | Article |
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| institution | DOAJ |
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| language | English |
| publishDate | 2024-12-01 |
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| spelling | doaj-art-0ebc7d2ae9dc42fba25170d436e4982f2025-08-20T02:53:23ZengMDPI AGBiomedicines2227-90592024-12-011212283310.3390/biomedicines12122833Spectrum of Pathogenic Variants of the ATP7B Gene and Genotype–Phenotype Correlation in Eastern Eurasian Patient Cohorts with Wilson’s DiseaseMikhail Garbuz0Elena Ovchinnikova1Anna Ovchinnikova2Valeriya Vinokurova3Yulya Aristarkhova4Olga Kuziakova5Mariya Mashurova6Vadim Kumeiko7School of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, RussiaSchool of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, RussiaSchool of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, RussiaSchool of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, RussiaSchool of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, RussiaSchool of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, RussiaSchool of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, RussiaSchool of Medicine and Life Sciences, Far Eastern Federal University, Vladivostok 690922, Russia<b>Background/Objectives:</b> Wilson’s disease (WD) (OMIM 277900) or hepatolenticular degeneration is an autosomal recessive disorder caused by impaired copper excretion with subsequent accumulation in the liver, brain, and other tissues of the body. The defects in copper metabolism are based on various pathogenic variants of the ATP7B gene encoding copper-transporting P-type ATPase. The aim of this work is to search for pathogenic variants of the ATP7B gene among Eastern Eurasian patient cohorts and to pick correlations between pathogenic variants, gender, age of onset of the disease, and the course of the disease. <b>Methods</b>: The material for the study was the biomaterial of 100 people. The search for mutations was carried out by Sanger sequencing. Multiple alignment of nucleotide sequences and their analysis was performed using the MEGA-X software. To study the genotype-phenotypic correlation, an analysis of the medical records of each patient was carried out. <b>Results</b>: Most common pathogenic variant (48%) in the sample is p.His1069Gln (c.3207C>A), located in exon 14 of the ATP7B gene. Pathogenic variants of p.Glu1064Lys (c.3190G>A)—20%—and p.Met769HisfsTer26 (c.2304insC)—8%—of exons 14 and 8 were also common. For patients with pathogenic alleles p.His1069Gln (c.3207C>A) and p.Glu1064Lys (c.3190G>A), typical deviations are mental and neurological manifestations of WD. In patients with the pathogenic allele p.Met769HisfsTer26 (c.2304insC), deviations are more characteristic of the liver and a combination of various symptoms that are atypical for WD. <b>Conclusions</b>: In this study, we were able to obtain differences in symptoms in patients with different pathogenic alleles of the ATP7B gene.https://www.mdpi.com/2227-9059/12/12/2833Wilson’s disease (WD)molecular genetic diagnostics |
| spellingShingle | Mikhail Garbuz Elena Ovchinnikova Anna Ovchinnikova Valeriya Vinokurova Yulya Aristarkhova Olga Kuziakova Mariya Mashurova Vadim Kumeiko Spectrum of Pathogenic Variants of the ATP7B Gene and Genotype–Phenotype Correlation in Eastern Eurasian Patient Cohorts with Wilson’s Disease Biomedicines Wilson’s disease (WD) molecular genetic diagnostics |
| title | Spectrum of Pathogenic Variants of the ATP7B Gene and Genotype–Phenotype Correlation in Eastern Eurasian Patient Cohorts with Wilson’s Disease |
| title_full | Spectrum of Pathogenic Variants of the ATP7B Gene and Genotype–Phenotype Correlation in Eastern Eurasian Patient Cohorts with Wilson’s Disease |
| title_fullStr | Spectrum of Pathogenic Variants of the ATP7B Gene and Genotype–Phenotype Correlation in Eastern Eurasian Patient Cohorts with Wilson’s Disease |
| title_full_unstemmed | Spectrum of Pathogenic Variants of the ATP7B Gene and Genotype–Phenotype Correlation in Eastern Eurasian Patient Cohorts with Wilson’s Disease |
| title_short | Spectrum of Pathogenic Variants of the ATP7B Gene and Genotype–Phenotype Correlation in Eastern Eurasian Patient Cohorts with Wilson’s Disease |
| title_sort | spectrum of pathogenic variants of the atp7b gene and genotype phenotype correlation in eastern eurasian patient cohorts with wilson s disease |
| topic | Wilson’s disease (WD) molecular genetic diagnostics |
| url | https://www.mdpi.com/2227-9059/12/12/2833 |
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