Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilep...
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2014
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| Acceso en línea: | https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13646745_v15_n1_p59_McFarland http://hdl.handle.net/20.500.12110/paper_13646745_v15_n1_p59_McFarland |
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paper:paper_13646745_v15_n1_p59_McFarland2023-06-08T16:11:49Z Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures Ataxia Epileptic seizures Phenotype-genotype correlation Repeat expansion Repeat interruptions SCA10 allele article Ataxin 10 gene clinical article family history gene genetic variability haplotype human nucleotide repeat phenotype priority journal risk factor seizure single nucleotide polymorphism spinocerebellar ataxia type 10 spinocerebellar degeneration Adult Alleles Cluster Analysis Cohort Studies DNA Repeat Expansion Epilepsy Female Genetic Association Studies Haplotypes Humans Male Mexico Microsatellite Repeats Middle Aged Phenotype Risk Sequence Analysis, DNA Spinocerebellar Ataxias Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed "ATCCT interruptions," experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confer a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling. © 2013 Springer-Verlag Berlin Heidelberg. 2014 https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13646745_v15_n1_p59_McFarland http://hdl.handle.net/20.500.12110/paper_13646745_v15_n1_p59_McFarland |
| institution |
Universidad de Buenos Aires |
| institution_str |
I-28 |
| repository_str |
R-134 |
| collection |
Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) |
| topic |
Ataxia Epileptic seizures Phenotype-genotype correlation Repeat expansion Repeat interruptions SCA10 allele article Ataxin 10 gene clinical article family history gene genetic variability haplotype human nucleotide repeat phenotype priority journal risk factor seizure single nucleotide polymorphism spinocerebellar ataxia type 10 spinocerebellar degeneration Adult Alleles Cluster Analysis Cohort Studies DNA Repeat Expansion Epilepsy Female Genetic Association Studies Haplotypes Humans Male Mexico Microsatellite Repeats Middle Aged Phenotype Risk Sequence Analysis, DNA Spinocerebellar Ataxias |
| spellingShingle |
Ataxia Epileptic seizures Phenotype-genotype correlation Repeat expansion Repeat interruptions SCA10 allele article Ataxin 10 gene clinical article family history gene genetic variability haplotype human nucleotide repeat phenotype priority journal risk factor seizure single nucleotide polymorphism spinocerebellar ataxia type 10 spinocerebellar degeneration Adult Alleles Cluster Analysis Cohort Studies DNA Repeat Expansion Epilepsy Female Genetic Association Studies Haplotypes Humans Male Mexico Microsatellite Repeats Middle Aged Phenotype Risk Sequence Analysis, DNA Spinocerebellar Ataxias Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures |
| topic_facet |
Ataxia Epileptic seizures Phenotype-genotype correlation Repeat expansion Repeat interruptions SCA10 allele article Ataxin 10 gene clinical article family history gene genetic variability haplotype human nucleotide repeat phenotype priority journal risk factor seizure single nucleotide polymorphism spinocerebellar ataxia type 10 spinocerebellar degeneration Adult Alleles Cluster Analysis Cohort Studies DNA Repeat Expansion Epilepsy Female Genetic Association Studies Haplotypes Humans Male Mexico Microsatellite Repeats Middle Aged Phenotype Risk Sequence Analysis, DNA Spinocerebellar Ataxias |
| description |
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed "ATCCT interruptions," experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confer a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling. © 2013 Springer-Verlag Berlin Heidelberg. |
| title |
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures |
| title_short |
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures |
| title_full |
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures |
| title_fullStr |
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures |
| title_full_unstemmed |
Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures |
| title_sort |
repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures |
| publishDate |
2014 |
| url |
https://bibliotecadigital.exactas.uba.ar/collection/paper/document/paper_13646745_v15_n1_p59_McFarland http://hdl.handle.net/20.500.12110/paper_13646745_v15_n1_p59_McFarland |
| _version_ |
1768545342500896768 |