@article{10902/35926,
year = {2025},
url = {https://hdl.handle.net/10902/35926},
abstract = {Introduction: 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.
Methods: 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.
Results: 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.
Conclusions: Our results confirm distinct allocations of SNPs associated to the expanded ATXN3, and accordingly the consideration of allele-specific therapies.},
organization = {Open Access funding enabled and organized by Projekt DEAL. This publication is an outcome of ESMI, an EU Joint Programme—Neurodegenerative Disease Research (JPND) project (see-www.jpnd.eu). The project is supported through the following funding organisations under the aegis of JPND: Germany, Federal Ministry of Education and Research (BMBF; funding codes 01ED1602A/B); Netherlands, The Netherlands Organisation for Health Research and Development; Portugal, Fundação para a Ciência e a Tecnologia (FCT); United Kingdom, Medical Research Council.},
publisher = {https://doi.org/10.1007/s00415-024-12829-9},
publisher = {Journal of Neurology, 2025, 272, 54},
title = {Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3},
author = {Lukas Elter, Tim and Sturm, Daniel and Santana, Magda M. and Schaprian, Tamara and Raposo, Mafalda and Vieira Melo, Ana Rosa and Lima, Manuela and Koyak, Berkan and Oender, Demet and Grobe-Einsler, Marcus and Lopes, Sara and Silva, Patrick and Pereira de Almeida, Luís and Giunti, Paola and García-Moreno, Héctor and Nethisinhe, Suran and Vries, Jeroen de and Van de Warrenburg, Bart P. and Infante Ceberio, Jon},
}