title: Comparing targeted exome and whole exome approaches for genetic diagnosis of neuromuscular disorders.
abstract: Massively parallel sequencing is rapidly becoming a widely used method in genetic diagnostics. However, there is still no clear consensus as to which approach can most efficiently identify the pathogenic mutations carried by a given patient, while avoiding false negative and false positive results. We developed a targeted exome approach (MyoPanel2) in order to optimize genetic diagnosis of neuromuscular disorders. Using this approach, we were able to analyse 306 genes known to be mutated in myopathies as well as in related disorders, obtaining 98.8% target sequence coverage at 20 ×. Moreover, MyoPanel2 was able to detect 99.7% of 11,467 known mutations responsible for neuromuscular disorders. We have then used several quality control parameters to compare performance of the targeted exome approach with that of whole exome sequencing. The results of this pilot study of 140 DNA samples suggest that targeted exome sequencing approach is an efficient genetic diagnostic test for most neuromuscular diseases.
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France.
authors.forename: Svetlana
authors.initials: S
authors.lastname: Gorokhova
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France; APHM, Department de Medical Genetics, Timone Children's Hospital, Marseille, France.
authors.forename: Mathieu
authors.initials: M
authors.lastname: Cerino
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Mathieu
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Courrier
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Desvignes
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France.
authors.forename: David
authors.initials: D
authors.lastname: Salgado
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Béroud
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France; APHM, Department de Medical Genetics, Timone Children's Hospital, Marseille, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Krahn
authors.affiliation: Aix Marseille University, INSERM, GMGF, UMR_S 910, 13385, Marseille, France.
authors.forename: Marc
authors.initials: M
authors.lastname: Bartoli
keywords: Gene panel; Genetic diagnosis; Massively parallel sequencing; Neuromuscular disorders; Targeted exome; Whole exome