Diagnostic capabilities of nanopore long‐read sequencing in muscular dystrophy

Many individuals with muscular dystrophies remain genetically undiagnosed despite clinical diagnostic testing, including exome sequencing. Some may harbor previously undetected structural variants (SVs) or cryptic splice sites. We enrolled 10 unrelated families: nine had muscular dystrophy but lacke...

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Bibliographic Details
Published in:Annals of clinical and translational neurology 2022-08, Vol.9 (8), p.1302-1309
Main Authors: Bruels, Christine C., Littel, Hannah R., Daugherty, Audrey L., Stafki, Seth, Estrella, Elicia A., McGaughy, Emily S., Truong, Don, Badalamenti, Jonathan P., Pais, Lynn, Ganesh, Vijay S., O'Donnell‐Luria, Anne, Stalker, Heather J., Wang, Yang, Collins, Christin, Behlmann, Andrea, Lemmers, Richard J. L. F., Maarel, Silvère M., Laine, Regina, Ghosh, Partha S., Darras, Basil T., Zingariello, Carla D., Pacak, Christina A., Kunkel, Louis M., Kang, Peter B.
Format: Article
Language:English
Subjects:
Asymptomatic
Biopsy
Brief Communication
Brief Communications
DNA methylation
Exome Sequencing
Genes
Genomes
Genomics
Humans
Muscular dystrophy
Muscular Dystrophy, Duchenne - diagnosis
Muscular Dystrophy, Duchenne - genetics
Nanopore Sequencing
Nanopores
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Description
Summary:Many individuals with muscular dystrophies remain genetically undiagnosed despite clinical diagnostic testing, including exome sequencing. Some may harbor previously undetected structural variants (SVs) or cryptic splice sites. We enrolled 10 unrelated families: nine had muscular dystrophy but lacked complete genetic diagnoses and one had an asymptomatic DMD duplication. Nanopore genomic long‐read sequencing identified previously undetected pathogenic variants in four individuals: an SV in DMD, an SV in LAMA2, and two single nucleotide variants in DMD that alter splicing. The DMD duplication in the asymptomatic individual was in tandem. Nanopore sequencing may help streamline genetic diagnostic approaches for muscular dystrophy.
ISSN:2328-9503
2328-9503
DOI:10.1002/acn3.51612