Milla-Neyra Karina, Araujo-Aliaga Ismael, Manrique-Enciso Carla, Sarapura-Castro Elison, Illanes-Manrique Maryenela, Veliz-Otani Diego, Saldarriaga-Mayo Ana, Medina-Colque Angel, Rios-Pinto Julia, Cornejo-Herrera Ivan, Rivera-Valdivia Andrea, F Mata Ignacio, Loesch Douglas, Lozano-Vasquez Leonel, Bordia Tanuja, O'Connor Timothy, Schüle Birgitt, Cornejo-Olivas Mario
Neurogenetics Research Center, Instituto Nacional de Ciencias Neurológicas, Lima, Peru.
Neurogenetics Working Group, Universidad Cientifica del Sur, Lima, Peru.
Cerebellum. 2025 Feb 7;24(2):44. doi: 10.1007/s12311-025-01795-1.
Spinocerebellar ataxia type 10 (SCA10) is a neurodegenerative disease predominant in Latin American individuals with Indigenous American ancestry. SCA10 is caused by an expansion of ATTCT repeat within the ATXN10 gene. Healthy individuals carry 9-32 ATTCT repeats, whereas SCA10 patients carry an expansion of 280 repeats and higher. Recently, intermediate alleles (over than 32 repeats) have been identified in healthy Peruvian Indigenous American individuals, with unclear significance. This study aims to characterize the variability of the ATTCT repeats within the ATXN10 gene across self-declared Indigenous American and Mestizo subpopulations from Peru. A total of 871 samples (754 Mestizo and 117 Indigenous American) were analyzed using PCR, and RP-PCR when suspecting apparent homozygosity due to larger alleles. 8.7% of the total of healthy individuals (76/871) carry at least one intermediate allele. The 14-repeat allele being the most common for both subpopulations (41.5%). Intermediate alleles were detected in the Peruvian population (4.5%) with a significantly higher frequency among self-declared Indigenous American compared to Mestizo, suggesting a possible association with the ethnic origin. The G allele at the SNP rs41524547 had a frequency of 51.39% in individuals with intermediate alleles, with not significantly difference between subpopulations. Further analysis should be performed to confirm the size and composition of ATTCT repeat tract, as well as the contribution of rs41524547 in SCA10.
10型脊髓小脑共济失调（SCA10）是一种主要在有美洲原住民血统的拉丁美洲个体中出现的神经退行性疾病。SCA10由ATXN10基因内ATTCT重复序列的扩增引起。健康个体携带9 - 32个ATTCT重复序列，而SCA10患者携带280个及以上的重复序列扩增。最近，在健康的秘鲁美洲原住民个体中发现了中间等位基因（超过32个重复序列），其意义尚不清楚。本研究旨在描述来自秘鲁自我宣称的美洲原住民和混血亚群体中ATXN10基因内ATTCT重复序列的变异性。共对871个样本（754个混血样本和117个美洲原住民样本）进行了PCR分析，当怀疑由于较大等位基因导致明显纯合子时进行反向PCR分析。健康个体总数的8.7%（76/871）携带至少一个中间等位基因。14个重复序列的等位基因在两个亚群体中最为常见（41.5%）。在秘鲁人群中检测到中间等位基因（4.5%），自我宣称的美洲原住民中的频率显著高于混血人群，提示可能与种族起源有关。SNP rs41524547处的G等位基因在携带中间等位基因的个体中的频率为51.39%，亚群体之间无显著差异。应进一步进行分析以确认ATTCT重复序列的大小和组成，以及rs41524547在SCA10中的作用。
