Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia)
Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalenc...
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Сибирские исследования
2020
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fttriple:oai:gotriple.eu:oai:doaj.org/article:4d4460f2b8e3489f9982971237dd0664 2023-05-15T18:06:42+02:00 Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) Goldfarb L.G. Platonov F.A. 2020-12-01 https://doi.org/10.33384/26587270.2019.02.008e https://siberes.ru/gallery/SCA_1_en.pdf https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 en ru eng rus Сибирские исследования doi:10.33384/26587270.2019.02.008e 2658-7181 2658-7270 https://siberes.ru/gallery/SCA_1_en.pdf https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 undefined Сибирские исследования, Vol 2, Iss 2, Pp 62-73 (2020) republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion demo psy Journal Article https://vocabularies.coar-repositories.org/resource_types/c_6501/ 2020 fttriple https://doi.org/10.33384/26587270.2019.02.008e 2023-01-22T19:29:36Z Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without ... Article in Journal/Newspaper Republic of Sakha Sakha Sakha Republic Yakutia Siberia Unknown Sakha Triplets ENVELOPE(-59.750,-59.750,-62.383,-62.383) Siberian Research 2 2 62 73 |
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language |
English Russian |
topic |
republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion demo psy |
spellingShingle |
republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion demo psy Goldfarb L.G. Platonov F.A. Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) |
topic_facet |
republic of sakha (yakutia) autosomal dominant spinocerebellar ataxia type 1 (sca1) atxn1 gene trinucleotide repeat expansion demo psy |
description |
Over the past several decades, more than 500 cases of Autosomal dominant spinocerebellar ataxia type 1 (SCA1) have been identified in the Republic of Sakha (Yakutia) of North-Eastern Siberia. The disease leads to long-term disability and death, making it a serious public health burden. The prevalence of SCA1 in the indigenous Sakha population has been steadily increasing since the 1970s. It has recently stabilized at a level of 45-53 per 100,000 due to efforts undertaken to limit its further spread. We describe results of a multi-year study of SCA1 in the Sakha population, including molecular genetics, distribution, clinical, electrophysiological and histopathological characteristics. Each studied patient had a mutation in the coding region of the ATXN1 gene on chromosome 6p22.3. The mutation presents as an uncontrolled increase in the number of trinucleotide CAG repeats from normal 25-32 to 39-72 with a loss of a CAT bridge in the middle of the CAG stretch. The number of continuous CAG triplets in the mutant ATXN1 gene correlates with the age of onset and the severity of the disease. The instability of this genomic segment is manifested in meiosis: the number of CAG repeats in a mutant gene increases in transmission from the father by an average of +3.04 repetitions and from the mother by +0.182 repetitions. The total number of repeats transmitted from one generation to another in the Sakha population is on average +1.614, which explains the increase in SCA1 prevalence. Patients from three spatially separate geographic regions of the Republic have the same haplotype, which confirms the origin of the mutation from a common ancestor about 37 generations ago. SCA1 patients in Mongolia, China and the U.S. show a different haplotype. To determine the potential of SCA1 for further spread, the fertility rates of the ATXN1 mutation carriers were evaluated and the Crow selection index calculated. The resulting score of 0.19 indicates that the mutation has little chance of being eliminated from the population without ... |
format |
Article in Journal/Newspaper |
author |
Goldfarb L.G. Platonov F.A. |
author_facet |
Goldfarb L.G. Platonov F.A. |
author_sort |
Goldfarb L.G. |
title |
Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) |
title_short |
Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) |
title_full |
Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) |
title_fullStr |
Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) |
title_full_unstemmed |
Genetic identification, clinical features and prevalence of Spinocerebellar ataxia type 1 in Sakha Republic (Yakutia) |
title_sort |
genetic identification, clinical features and prevalence of spinocerebellar ataxia type 1 in sakha republic (yakutia) |
publisher |
Сибирские исследования |
publishDate |
2020 |
url |
https://doi.org/10.33384/26587270.2019.02.008e https://siberes.ru/gallery/SCA_1_en.pdf https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 |
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ENVELOPE(-59.750,-59.750,-62.383,-62.383) |
geographic |
Sakha Triplets |
geographic_facet |
Sakha Triplets |
genre |
Republic of Sakha Sakha Sakha Republic Yakutia Siberia |
genre_facet |
Republic of Sakha Sakha Sakha Republic Yakutia Siberia |
op_source |
Сибирские исследования, Vol 2, Iss 2, Pp 62-73 (2020) |
op_relation |
doi:10.33384/26587270.2019.02.008e 2658-7181 2658-7270 https://siberes.ru/gallery/SCA_1_en.pdf https://doaj.org/article/4d4460f2b8e3489f9982971237dd0664 |
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undefined |
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https://doi.org/10.33384/26587270.2019.02.008e |
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Siberian Research |
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2 |
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62 |
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73 |
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