High-resolution repeat structure analysis in myotonic dystrophy type 2 diagnostics using short-read whole genome sequencing

被引：0

作者：

Lojova, Ingrid ^{[1
,2
,3
]}

Kucharik, Marcel ^{[1
,2
,4
]}

Zatkova, Andrea ^{[1
]}

Balaz, Andrej ^{[1
,4
]}

Pös, Zuzana ^{[1
,4
]}

Tarova, Eva Tothova ^{[1
]}

Kadasi, Ludevit ^{[1
,3
]}

Budis, Jaroslav ^{[2
,4
,5
]}

Szemes, Tomas ^{[2
,3
,4
]}

Radvanszky, Jan ^{[1
,2
,3
,6
]}

机构：

[1] Institute of Clinical and Translational Research, Biomedical Research Center of the Slovak Academy of Sciences, Dúbravská Cesta 9, Karlova Ves, Bratislava

[2] Comenius University Science Park, Ilkovičova 8, Karlova Ves, Bratislava, 841

[3] Department of Molecular Biology, Faculty of Natural Sciences, Comenius University, Ilkovičova 6, Karlova Ves, Bratislava

[4] Geneton Ltd., Ilkovičova 8, Bratislava

[5] Genovisio Ltd., Ilkovičova 8, Karlova Ves, Bratislava

[6] G2 Consulting Slovakia Ltd., Slnečnicová 559/5, Hviezdoslavov

来源：

Analytical Biochemistry | 2025年 / 700卷

基金：

欧盟地平线“2020”;

关键词：

Massively parallel sequencing; Myotonic dystrophy type 2; Repeat expansion disorders; Tandem repeats; Whole genome sequencing;

D O I：

10.1016/j.ab.2025.115793

中图分类号：

学科分类号：

摘要：

Background/Objectives: Diagnostic possibilities for myotonic dystrophy type 2 (DM2) are constantly evolving in order to achieve more accurate and faster diagnosis. Whole genome sequencing (WGS), together with specialized tandem repeat (TR) genotyping bioinformatic tools, represent a breakthrough technology in molecular diagnostics. We decided to characterize new opportunities and challenges in WGS-based DM2 molecular diagnostics. Methods: WGS data were obtained from 50 individuals, including five DM2 patients, and one individual carrying a premutation range allele. TR characterization was performed using a modified version of the Dante tool, with results validated by conventional PCR and repeat-primed PCR. Results: We used WGS to identify all of the expansion-range DM2 alleles, together with the premutation-range allele. Compared to conventional methods, WGS was more efficient for a detailed sequence structure characterization of the normal-range alleles, and phasing of the entire CNBP-complex motif. A 97 % genotyping concordance rate was achieved between the conventional methods and the WGS-derived results, with discrepancies mainly based on single-repeat differences in the genotypes. The stutter effect introduced some uncertainty in both methods. Conclusion: Short-read WGS offers significant potential for DM2 diagnostics by enabling precise repeat motif characterization and may also apply to other tandem repeat disorders (TRDs). © 2025 The Authors

引用

共 32 条

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