Diagnostic capabilities of nanopore long-read sequencing in muscular dystrophy.
Christine C BruelsHannah R LittelAudrey L DaughertySeth StafkiElicia A EstrellaEmily S McGaughyDon TruongJonathan P BadalamentiLynn PaisVijay S GaneshAnne O'Donnell-LuriaHeather J StalkerYang WangChristin CollinsAndrea BehlmannRichard J L F LemmersSilvère M van der MaarelRegina LainePartha S GhoshBasil T DarrasCarla D ZingarielloChristina A PacakLouis M KunkelPeter B KangPublished in: Annals of clinical and translational neurology (2022)
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.