Our study investigated the presence of regional differences in hexanucleotide repeat number in postmortem brain tissues of 2 patients with X-linked dystonia-parkinsonism (XDP), a combined dystonia-parkinsonism syndrome modified by a (CCCTCT)_n repeat within the causal SINE-VNTR-Alu retrotransposon insertion in the TAF1 gene.

Genomic DNA was extracted from blood and postmortem brain samples, including the basal ganglia and cortex from both patients and from the cerebellum, midbrain, and pituitary gland from 1 patient. Repeat sizing was performed using fragment analysis, small-pool PCR-based Southern blotting, and Oxford nanopore sequencing.

The basal ganglia (p < 0.001) and cerebellum (p < 0.001) showed higher median repeat numbers and higher degrees of repeat instability compared with blood.

Somatic repeat instability may predominate in brain regions selectively affected in XDP, thereby hinting at its potential role in disease manifestation and modification.

我们的研究调查了 2 名 X 连锁肌张力障碍-帕金森症 (XDP) 患者死后脑组织中六核苷酸重复数的区域差异，这是一种由因果 SINE-VNTR 内的(CCCTCT) _n重复修饰的联合肌张力障碍-帕金森综合征- Alu反转录转座子插入TAF1基因。

从血液和死后脑样本中提取基因组 DNA，包括来自两名患者的基底神经节和皮质，以及来自 1 名患者的小脑、中脑和垂体。使用片段分析、基于小池 PCR 的 Southern 印迹和牛津纳米孔测序进行重复大小调整。

与血液相比，基底神经节 ( p < 0.001) 和小脑 ( p < 0.001) 显示出更高的中位重复次数和更高程度的重复不稳定性。

体细胞重复不稳定性可能在受 XDP 选择性影响的大脑区域中占主导地位，从而暗示其在疾病表现和改变中的潜在作用。