Annals of Clinical and Translational Neurology (Aug 2022)
Diagnostic capabilities of nanopore long‐read sequencing in muscular dystrophy
- Christine C. Bruels,
- Hannah R. Littel,
- Audrey L. Daugherty,
- Seth Stafki,
- Elicia A. Estrella,
- Emily S. McGaughy,
- Don Truong,
- Jonathan P. Badalamenti,
- Lynn Pais,
- Vijay S. Ganesh,
- Anne O'Donnell‐Luria,
- Heather J. Stalker,
- Yang Wang,
- Christin Collins,
- Andrea Behlmann,
- Richard J. L. F. Lemmers,
- Silvère M. van derMaarel,
- Regina Laine,
- Partha S. Ghosh,
- Basil T. Darras,
- Carla D. Zingariello,
- Christina A. Pacak,
- Louis M. Kunkel,
- Peter B. Kang
Affiliations
- Christine C. Bruels
- Paul and Sheila Wellstone Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School Minneapolis Minnesota 55455
- Hannah R. Littel
- Paul and Sheila Wellstone Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School Minneapolis Minnesota 55455
- Audrey L. Daugherty
- Paul and Sheila Wellstone Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School Minneapolis Minnesota 55455
- Seth Stafki
- Paul and Sheila Wellstone Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School Minneapolis Minnesota 55455
- Elicia A. Estrella
- Department of Neurology Boston Children's Hospital Boston Massachusetts
- Emily S. McGaughy
- Division of Pediatric Neurology, Department of Pediatrics University of Florida College of Medicine Gainesville Florida 32610
- Don Truong
- Paul and Sheila Wellstone Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School Minneapolis Minnesota 55455
- Jonathan P. Badalamenti
- University of Minnesota Genomics Center University of Minnesota Minneapolis Minnesota 55455
- Lynn Pais
- Division of Genetics and Genomics Boston Children's Hospital Boston Massachusetts
- Vijay S. Ganesh
- Division of Genetics and Genomics Boston Children's Hospital Boston Massachusetts
- Anne O'Donnell‐Luria
- Division of Genetics and Genomics Boston Children's Hospital Boston Massachusetts
- Heather J. Stalker
- Division of Genetics, Department of Pediatrics University of Florida College of Medicine Gainesville Florida 32610
- Yang Wang
- PerkinElmer Genomics Pittsburgh Pennsylvania
- Christin Collins
- PerkinElmer Genomics Pittsburgh Pennsylvania
- Andrea Behlmann
- PerkinElmer Genomics Pittsburgh Pennsylvania
- Richard J. L. F. Lemmers
- Department of Human Genetics Leiden University Medical Center Leiden Netherlands
- Silvère M. van derMaarel
- Department of Human Genetics Leiden University Medical Center Leiden Netherlands
- Regina Laine
- Department of Neurology Boston Children's Hospital Boston Massachusetts
- Partha S. Ghosh
- Department of Neurology Boston Children's Hospital Boston Massachusetts
- Basil T. Darras
- Department of Neurology Boston Children's Hospital Boston Massachusetts
- Carla D. Zingariello
- Division of Pediatric Neurology, Department of Pediatrics University of Florida College of Medicine Gainesville Florida 32610
- Christina A. Pacak
- Paul and Sheila Wellstone Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School Minneapolis Minnesota 55455
- Louis M. Kunkel
- Division of Genetics and Genomics Boston Children's Hospital Boston Massachusetts
- Peter B. Kang
- Paul and Sheila Wellstone Muscular Dystrophy Center and Department of Neurology University of Minnesota Medical School Minneapolis Minnesota 55455
- DOI
- https://doi.org/10.1002/acn3.51612
- Journal volume & issue
-
Vol. 9,
no. 8
pp. 1302 – 1309
Abstract
Abstract 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.
