title: RNAseq analysis for the diagnosis of muscular dystrophy.
abstract: The precise genetic cause remains elusive in nearly 50% of patients with presumed neurogenetic disease, representing a significant barrier for clinical care. This is despite significant advances in clinical genetic diagnostics, including the application of whole-exome sequencing and next-generation sequencing-based gene panels. In this study, we identify a deep intronic mutation in the DMD gene in a patient with muscular dystrophy using both conventional and RNAseq-based transcriptome analyses. The implications of our data are that noncoding mutations likely comprise an important source of unresolved genetic disease and that RNAseq is a powerful platform for detecting such mutations.
authors.affiliation: Division of Neurology Hospital for Sick Children Toronto Ontario Canada M5G A04; Program of Genetics and Genome Biology Hospital for Sick Children Toronto Ontario Canada M5G A04; Department of Paediatrics University of Toronto Toronto Ontario Canada M5G AO4.
authors.forename: Hernan
authors.initials: H
authors.lastname: Gonorazky
authors.affiliation: Program of Genetics and Genome Biology Hospital for Sick Children Toronto Ontario Canada M5G A04; Department of Molecular Genetics University of Toronto Toronto Ontario Canada M5G AO4.
authors.forename: Minggao
authors.initials: M
authors.lastname: Liang
authors.affiliation: Analytic and Translational Genetics Unit Massachusetts General Hospital Boston Massachusetts 02114; Program in Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge Massachusetts.
authors.forename: Beryl
authors.initials: B
authors.lastname: Cummings
authors.affiliation: Analytic and Translational Genetics Unit Massachusetts General Hospital Boston Massachusetts 02114; Program in Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge Massachusetts.
authors.forename: Monkol
authors.initials: M
authors.lastname: Lek
authors.affiliation: Program of Genetics and Genome Biology Hospital for Sick Children Toronto Ontario Canada M5G A04.
authors.forename: Johann
authors.initials: J
authors.lastname: Micallef
authors.affiliation: Pediatric Laboratory Medicine Hospital for Sick Children Toronto Ontario Canada M5G A04.
authors.forename: Cynthia
authors.initials: C
authors.lastname: Hawkins
authors.affiliation: Pediatric Laboratory Medicine Hospital for Sick Children Toronto Ontario Canada M5G A04.
authors.forename: Raveen
authors.initials: R
authors.lastname: Basran
authors.affiliation: Program of Genetics and Genome Biology Hospital for Sick Children Toronto Ontario Canada M5G A04; Department of Paediatrics University of Toronto Toronto Ontario Canada M5G AO4; Department of Molecular Genetics University of Toronto Toronto Ontario Canada M5G AO4.
authors.forename: Ronald
authors.initials: R
authors.lastname: Cohn
authors.affiliation: Program of Genetics and Genome Biology Hospital for Sick Children Toronto Ontario Canada M5G A04; Department of Molecular Genetics University of Toronto Toronto Ontario Canada M5G AO4.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Wilson
authors.affiliation: Analytic and Translational Genetics Unit Massachusetts General Hospital Boston Massachusetts 02114; Program in Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge Massachusetts.
authors.forename: Daniel
authors.initials: D
authors.lastname: MacArthur
authors.affiliation: Pediatric Laboratory Medicine Hospital for Sick Children Toronto Ontario Canada M5G A04.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.affiliation: Program of Genetics and Genome Biology Hospital for Sick Children Toronto Ontario Canada M5G A04; Department of Molecular Genetics University of Toronto Toronto Ontario Canada M5G AO4; Pediatric Laboratory Medicine Hospital for Sick Children Toronto Ontario Canada M5G A04.
authors.forename: Peter N
authors.initials: PN
authors.lastname: Ray
authors.affiliation: Division of Neurology Hospital for Sick Children Toronto Ontario Canada M5G A04; Program of Genetics and Genome Biology Hospital for Sick Children Toronto Ontario Canada M5G A04; Department of Paediatrics University of Toronto Toronto Ontario Canada M5G AO4; Department of Molecular Genetics University of Toronto Toronto Ontario Canada M5G AO4.
authors.forename: James J
authors.initials: JJ
authors.lastname: Dowling