Brain Regional Differences in Hexanucleotide Repeat Length in X-Linked Dystonia-Parkinsonism Using Nanopore Sequencing.

Abstract

OBJECTIVE:

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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

• Authors: Charles Jourdan Reyes, Björn-Hergen Laabs, Susen Schaake, Theresa Lüth, Raphaela Ardicoglu, Aleksandar Rakovic, Karen Grütz, Daniel Alvarez-Fischer, Roland Dominic Jamora, Raymond L Rosales, Imke Weyers, Inke R König, Norbert Brüggemann, Christine Klein, Valerija Dobricic, Ana Westenberger, Joanne Trinh
• Journal: Neurology. Genetics (Neurol Genet) Vol. 7 Issue 4 Pg. e608 (Aug 2021) ISSN: 2376-7839 [Print] United States
• PMID: 34250228 (Publication Type: Journal Article)
• Copyright: Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.