TY  - JOUR
AU  - Elter, Tim-Lukas
AU  - Sturm, Daniel
AU  - Santana, Magda M
AU  - Schaprian, Tamara
AU  - Raposo, Mafalda
AU  - Melo, Ana Rosa Vieira
AU  - Lima, Manuela
AU  - Koyak, Berkan
AU  - Oender, Demet
AU  - Grobe-Einsler, Marcus
AU  - Lopes, Sara
AU  - Silva, Patrick
AU  - de Almeida, Luís Pereira
AU  - Giunti, Paola
AU  - Garcia-Moreno, Hector
AU  - Nethisinhe, Suran
AU  - de Vries, Jeroen
AU  - van de Warrenburg, Bart P
AU  - van Gaalen, Judith
AU  - Synofzik, Matthis
AU  - Schöls, Ludger
AU  - Reetz, Kathrin
AU  - Erdlenbruch, Friedrich
AU  - Jacobi, Heike
AU  - Infante, Jon
AU  - Riess, Olaf
AU  - Klockgether, Thomas
AU  - Faber, Jennifer
AU  - Hübener-Schmid, Jeannette
TI  - Regional distribution of polymorphisms associated to the disease-causing gene of spinocerebellar ataxia type 3.
JO  - Journal of neurology
VL  - 272
IS  - 1
SN  - 0367-004X
CY  - Heidelberg
PB  - Springer
M1  - DZNE-2024-01420
SP  - 54
PY  - 2025
AB  - 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.
KW  - Humans
KW  - Machado-Joseph Disease: genetics
KW  - Male
KW  - Female
KW  - Ataxin-3: genetics
KW  - Polymorphism, Single Nucleotide
KW  - Middle Aged
KW  - Adult
KW  - Nerve Tissue Proteins: genetics
KW  - Repressor Proteins: genetics
KW  - Aged
KW  - Genotype
KW  - Cohort Studies
KW  - Nuclear Proteins: genetics
KW  - Gene Frequency
KW  - Haplotypes
KW  - Young Adult
KW  - ATXN3 (Other)
KW  - ASO (Other)
KW  - Polymorphism (Other)
KW  - SCA3 (Other)
KW  - SNP (Other)
KW  - Spinocerebellar ataxia (Other)
KW  - Ataxin-3 (NLM Chemicals)
KW  - ATXN3 protein, human (NLM Chemicals)
KW  - Nerve Tissue Proteins (NLM Chemicals)
KW  - Repressor Proteins (NLM Chemicals)
KW  - Nuclear Proteins (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C2  - pmc:PMC11638412
C6  - pmid:39666145
DO  - DOI:10.1007/s00415-024-12829-9
UR  - https://pub.dzne.de/record/273946
ER  -