Open AccessDiagnostic capabilities of nanopore long‐read sequencing in muscular dystrophy
Author(s) -
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'DonnellLuria 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.
Publication year - 2022
Publication title -
annals of clinical and translational neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.824
H-Index - 42
ISSN - 2328-9503
DOI - 10.1002/acn3.51612
Subject(s) - muscular dystrophy , medicine , exome sequencing , gene duplication , nanopore sequencing , genetics , duchenne muscular dystrophy , genetic diagnosis , genetic testing , rna splicing , computational biology , bioinformatics , dna sequencing , gene , mutation , biology , rna
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.