Science News: Long-Read Sequencing Improves Diagnostic Rate in Neuromuscular Disorders

Published October 28, 2024

Science News

Submitted by: Justin Willer, MD
Edited by: Milvia Pleitez, MD

Citation: Owusu R, Savarese M. Long-read sequencing improves diagnostic rate in neuromuscular disorders. Acta Myol. 2023;42(4):123-128. Published 2023 Dec 20. doi:10.36185/2532-1900-394
 
Summary: Short read sequencing has limitations including inaccurate genome assembly, an inability to detect large structural variants and variants in hard to sequence areas, such as highly repetitive sequences.  

Long read sequencing reads DNA from 1,000 bases to several kilobases. It can detect large and small structural variants, repeat expansions and epigenetic modifications, such as DNA methylation. It eliminates bias associated with DNA amplification as single DNA molecules can be sequenced and increases accuracy and reduces the time need for the molecular diagnosis of NM disorders. It has been successful in detecting novel rare structural variants particular in the Duchenne muscular dystrophy (DMD) gene in patients with DMD.

It has also been used for diagnosing patients with oculopharyngeal MD after short read sequencing failed to find a pathogenic variant. It has also been used to identify C4Z4 repeats in Facioscapulohumeral muscular dystrophy (FSHD). It has also been helpful in diagnosing repeat expansions in Myotonic dystrophy type 1. 

Long read sequencing has also been used for haplotyping in spinal muscular atrophy and allowed the detection of silent carriers and helped identify inheritance patterns of survival motor neuron (SMN) 1 and SMN2 haplotypes in most of the families of silent carriers.

Comments: A powerful new tool for the molecular diagnosis of NM disorders.