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

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

doi:10.1212/NXG.0000000000000608

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

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

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.

Original language	English
Journal	Neurology Genetics
Volume	7
Issue number	4
Pages (from-to)	e608
ISSN	2376-7839
DOIs	https://doi.org/10.1212/NXG.0000000000000608
Publication status	Published - 08.2021

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Reyes, C. J., Laabs, B.-H., Schaake, S., Lüth, T., Ardicoglu, R., Rakovic, A., Grütz, K., Alvarez-Fischer, D., Jamora, R. D., Rosales, R. L., Weyers, I., König, I. R., Brüggemann, N., Klein, C., Dobricic, V., Westenberger, A., & Trinh, J. (2021). Brain Regional Differences in Hexanucleotide Repeat Length in X-Linked Dystonia-Parkinsonism Using Nanopore Sequencing. Neurology Genetics, 7(4), e608. https://doi.org/10.1212/NXG.0000000000000608

@article{c20070b85069428e942122a402b59896,

title = "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.",

author = "Reyes, {Charles Jourdan} and Bj{\"o}rn-Hergen Laabs and Susen Schaake and Theresa L{\"u}th and Raphaela Ardicoglu and Aleksandar Rakovic and Karen Gr{\"u}tz and Daniel Alvarez-Fischer and Jamora, {Roland Dominic} and Rosales, {Raymond L} and Imke Weyers and K{\"o}nig, {Inke R} and Norbert Br{\"u}ggemann and Christine Klein and Valerija Dobricic and Ana Westenberger and Joanne Trinh",

note = "Copyright {\textcopyright} 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.",

year = "2021",

month = aug,

doi = "10.1212/NXG.0000000000000608",

language = "English",

volume = "7",

pages = "e608",

journal = "Neurology Genetics",

issn = "2376-7839",

number = "4",

}

Reyes, CJ, Laabs, B-H, Schaake, S, Lüth, T, Ardicoglu, R, Rakovic, A, Grütz, K , Alvarez-Fischer, D, Jamora, RD, Rosales, RL, Weyers, I , König, IR , Brüggemann, N , Klein, C , Dobricic, V , Westenberger, A & Trinh, J 2021, 'Brain Regional Differences in Hexanucleotide Repeat Length in X-Linked Dystonia-Parkinsonism Using Nanopore Sequencing', Neurology Genetics, vol. 7, no. 4, pp. e608. https://doi.org/10.1212/NXG.0000000000000608

TY - JOUR

T1 - Brain Regional Differences in Hexanucleotide Repeat Length in X-Linked Dystonia-Parkinsonism Using Nanopore Sequencing

AU - Reyes, Charles Jourdan

AU - Laabs, Björn-Hergen

AU - Schaake, Susen

AU - Lüth, Theresa

AU - Ardicoglu, Raphaela

AU - Rakovic, Aleksandar

AU - Grütz, Karen

AU - Alvarez-Fischer, Daniel

AU - Jamora, Roland Dominic

AU - Rosales, Raymond L

AU - Weyers, Imke

AU - König, Inke R

AU - Brüggemann, Norbert

AU - Klein, Christine

AU - Dobricic, Valerija

AU - Westenberger, Ana

AU - Trinh, Joanne

PY - 2021/8

Y1 - 2021/8

N2 - 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.

AB - 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.

U2 - 10.1212/NXG.0000000000000608

DO - 10.1212/NXG.0000000000000608

M3 - Journal articles

C2 - 34250228

SN - 2376-7839

VL - 7

SP - e608

JO - Neurology Genetics

JF - Neurology Genetics

IS - 4

ER -

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

Abstract

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