Targeted long-read sequencing enables comprehensive analysis of the genetic and epigenetic landscape of inherited myopathies
Таргетное секвенирование с длинными чтениями позволяет всесторонне анализировать генетический и эпигенетический ландшафт наследственных миопатий
2026-07-04
SCID: 54.1/xwc3ba2m
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epigenetic signaturesinherited myopathiesrepeat expansionsstructural variantstargeted long-read sequencing
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Abstract (AI)
Abstract The genetic variants that cause inherited myopathies vary widely in type, size and sequence context, encompassing small sequence variants, large structural variants, repeat expansions, and more complex events, such as the D4Z4 macrosatellite contraction and hypomethylation that causes facioscapulohumeral muscular dystrophy. Many of these are challenging to characterise using next-generation sequencing and other older molecular technologies. To address this, we developed a targeted long-read sequencing assay and bioinformatics analysis framework that captures the full suite of genes, variants and epigenetic signatures currently implicated in inherited myopathies. Applying this to a cohort of myopathy patients, we demonstrate the analytical validity of our approach and its improved accuracy and resolution compared to existing methods. Our assay led to new genetic diagnoses in 35.5% (11/31) of patients who remained undiagnosed after standard clinical genetic testing. This methodology constitutes a single streamlined assay for comprehensive genetic and epigenetic characterisation of inherited myopathies.
Key Findings
1
A targeted long-read sequencing assay and bioinformatics framework was developed to capture genes, variants, and epigenetic signatures implicated in inherited myopathies.
2
Applied to a cohort of myopathy patients, the method demonstrated analytical validity and improved accuracy and resolution compared to existing methods.
3
The assay can characterize a wide spectrum of variant types difficult for short-read NGS, including small sequence variants, large structural variants, repeat expansions, and complex events like D4Z4 macrosatellite contraction and hypomethylation.
4
The assay provided new genetic diagnoses in 35.5% (11/31) of patients who were undiagnosed after standard clinical genetic testing.
5
This single streamlined assay enables comprehensive genetic and epigenetic characterization of inherited myopathies within one workflow.
Research Object
Targeted long-read sequencing assay and bioinformatics analysis framework for genes implicated in inherited myopathies
Research Subject
Comprehensive detection and characterisation of genetic variants (small variants, large structural variants, repeat expansions, complex events) and epigenetic signatures (e.g., methylation/D4Z4 hypomethylation) underlying inherited myopathies, and the assay's analytical validity and diagnostic yield versus standard methods
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2026-07-04
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