Nanopore sequencing combined with adaptive sampling and NanoExpansion enables accurate characterization of repeat expansion disorders

Expansion repeat disorders are caused by abnormal expansions of short tandem repeats (STRs). We evaluated targeted long-read nanopore sequencing for comprehensive characterization of STR expansions in 132 participants, including patients with myotonic dystrophy type 1 (DM1, n = 51) and DM2 ( n = 3) already characterized by Southern blot, C9orf72 -associated amyotrophic lateral sclerosis (ALS n = 11) evaluated by...

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No actionable change for current audiology practice; this is a genomics methods paper with potential future relevance to genetic diagnosis of hearing and balance disorders but no immediate clinical application.

Improved genetic characterization of repeat expansion disorders could eventually expand diagnostic options for audiologists managing hereditary hearing loss and balance conditions.

1. 01Nanopore long-read sequencing combined with adaptive sampling improved detection of short tandem repeat expansions.
2. 02The NanoExpansion tool was developed specifically to analyse and characterise these repeat regions from nanopore data.
3. 03Some repeat expansion disorders (e.g., spinocerebellar ataxias, Friedreich's ataxia) have auditory and vestibular phenotypes.
4. 04The method offers advantages over short-read sequencing for complex, repetitive genomic regions.
5. 05Published in NAR Genomics and Bioinformatics; methodological/genomics focus rather than clinical audiology.

PMID

42840349

DOI

10.1093/nargab/lqag117.

Journal

NAR Genomics and Bioinformatics

Publication type

research_article

Evidence level

2b

Population

Genomic samples from patients with known or suspected repeat expansion disorders

Intervention

Targeted long-read nanopore sequencing with adaptive sampling and NanoExpansion bioinformatics tool

Comparator

Standard short-read sequencing methods