title: Myopathology in the times of modern genetics.
abstract: The advent of Next Generation Sequencing (NGS) technologies has accelerated the rate of novel disease gene discovery. Analysis of the large datasets generated by whole exome sequencing, whole genome sequencing, and other NGS approaches poses a challenge to physicians and pathologists searching for disease causing variants amongst the 50 000-3 million polymorphisms typically seen in these datasets. This review describes strategies that successfully combine classical neuropathological investigation (e.g. histology, immunostaining and electron microscopy) with modern NGS technologies to pinpoint the underlying genetic cause of a disease. We describe filtering techniques and free online bioinformatic tools that can help physicians and researchers establish a molecular diagnosis from NGS data. The ethical issues raised by NGS data are outlined. We provide specific examples that illustrate how traditional and contemporary approaches integrate to solve a difficult diagnosis or to correct initially wrong assumptions based on data generated from one method alone.
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Berlin, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Schuelke
authors.affiliation: Department of Neuropediatrics and NeuroCure Clinical Research Center, Charité-Universitätsmedizin, Berlin, Germany.|Max-Delbrück-Center for Molecular Medicine, Berlin, Germany.
authors.forename: N C
authors.initials: NC
authors.lastname: Øien
authors.affiliation: Department of Pathology and Genetics, Institute of Biomedicine, University of Gothenburg, Gothenburg, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Oldfors
mesh_terms: D005821:Genetic Techniques; D009468:Neuromuscular Diseases / Q000235:genetics*
keywords: applied bioinformatics; disease classification; genetic variant interpretation; muscle; next generation sequencing; rare disease