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@ARTICLE{Elter:273946,
author = {Elter, Tim-Lukas and Sturm, Daniel and Santana, Magda M and
Schaprian, Tamara and Raposo, Mafalda and Melo, Ana Rosa
Vieira and Lima, Manuela and Koyak, Berkan and Oender, Demet
and Grobe-Einsler, Marcus and Lopes, Sara and Silva, Patrick
and de Almeida, Luís Pereira and Giunti, Paola and
Garcia-Moreno, Hector and Nethisinhe, Suran and de Vries,
Jeroen and van de Warrenburg, Bart P and van Gaalen, Judith
and Synofzik, Matthis and Schöls, Ludger and Reetz, Kathrin
and Erdlenbruch, Friedrich and Jacobi, Heike and Infante,
Jon and Riess, Olaf and Klockgether, Thomas and Faber,
Jennifer and Hübener-Schmid, Jeannette},
collaboration = {group, ESMI study},
othercontributors = {Timmann, Dagmar and Thieme, Andreas},
title = {{R}egional distribution of polymorphisms associated to the
disease-causing gene of spinocerebellar ataxia type 3.},
journal = {Journal of neurology},
volume = {272},
number = {1},
issn = {0367-004X},
address = {Heidelberg},
publisher = {Springer},
reportid = {DZNE-2024-01420},
pages = {54},
year = {2025},
abstract = {Knowledge about the distribution and frequency of the
respective haplotypes on the wildtype and mutant allele is
highly relevant in the context of future gene therapy
clinical studies in Spinocerebellar Ataxia Type 3, the most
common autosomal dominantly inherited ataxia. Single
nucleotide polymorphisms associated to the disease-causing
gene, ATXN3, have been determined. We wanted to investigate
the frequency and regional distribution of two intragenic
single nucleotide polymorphisms (SNPs) in a large European
SCA3 cohort and their relation to the clinical phenotype.The
genotypes of the two polymorphisms at base pair positions
987 and 1118 of the ATXN3 were determined for their
co-localization on the normal and expanded allele,
respectively, in 286 SCA3 mutation carriers and 117 healthy
controls from 11 European sites.The distribution of
genotypes on the expanded allele differed from those of the
wildtype allele of SCA3 mutation carriers and of healthy
controls, and was mainly influenced by the regional origin.
In our cohort, no particular clinical phenotype was
associated with any specific haplotype.Our results confirm
distinct allocations of SNPs associated to the expanded
ATXN3, and accordingly the consideration of allele-specific
therapies.},
keywords = {Humans / Machado-Joseph Disease: genetics / Male / Female /
Ataxin-3: genetics / Polymorphism, Single Nucleotide /
Middle Aged / Adult / Nerve Tissue Proteins: genetics /
Repressor Proteins: genetics / Aged / Genotype / Cohort
Studies / Nuclear Proteins: genetics / Gene Frequency /
Haplotypes / Young Adult / ATXN3 (Other) / ASO (Other) /
Polymorphism (Other) / SCA3 (Other) / SNP (Other) /
Spinocerebellar ataxia (Other) / Ataxin-3 (NLM Chemicals) /
ATXN3 protein, human (NLM Chemicals) / Nerve Tissue Proteins
(NLM Chemicals) / Repressor Proteins (NLM Chemicals) /
Nuclear Proteins (NLM Chemicals)},
cin = {Clinical Research (Bonn) / Patient Studies (Bonn) / AG
Gasser},
ddc = {610},
cid = {I:(DE-2719)1011001 / I:(DE-2719)1011101 /
I:(DE-2719)1210000},
pnm = {353 - Clinical and Health Care Research (POF4-353)},
pid = {G:(DE-HGF)POF4-353},
typ = {PUB:(DE-HGF)16},
pmc = {pmc:PMC11638412},
pubmed = {pmid:39666145},
doi = {10.1007/s00415-024-12829-9},
url = {https://pub.dzne.de/record/273946},
}