title: Utility of a next-generation sequencing-based gene panel investigation in German patients with genetically unclassified limb-girdle muscular dystrophy.
abstract: Limb-girdle muscular dystrophies (LGMDs) are genetically heterogeneous and the diagnostic work-up including conventional genetic testing using Sanger sequencing remains complex and often unsatisfactory. We performed targeted sequencing of 23 LGMD-related genes and 15 genes in which alterations result in a similar phenotype in 58 patients with genetically unclassified LGMDs. A genetic diagnosis was possible in 19 of 58 patients (33 %). LGMD2A was the most common form, followed by LGMD2L and LGMD2I. In two patients, pathogenic mutations were identified in genes that are not classified as LGMD genes (glycogen branching enzyme and valosin-containing protein). Thus, a focused next-generation sequencing-based gene panel is a rather satisfactory tool for the diagnosis in unclassified LGMDs.
authors.affiliation: Genetikum, Neu-Ulm, Germany.|Division of Neurophysiology, Universität Ulm, Ulm, Germany.
authors.forename: Marius
authors.initials: M
authors.lastname: Kuhn
authors.affiliation: Genetikum, Neu-Ulm, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Gläser
authors.affiliation: Klinik und Poliklinik für Neurologie, Universität Halle-Wittenberg, Halle, Germany.
authors.forename: Pushpa Raj
authors.initials: PR
authors.lastname: Joshi
authors.affiliation: Klinik und Poliklinik für Neurologie, Universität Halle-Wittenberg, Halle, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Zierz
authors.affiliation: Friedrich-Baur-Institut, Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Wenninger
authors.affiliation: Friedrich-Baur-Institut, Neurologische Klinik, Ludwig-Maximilians-Universität München, Munich, Germany.
authors.forename: Benedikt
authors.initials: B
authors.lastname: Schoser
authors.affiliation: Klinik und Poliklinik für Neurologie, Universität Halle-Wittenberg, Halle, Germany. deschauer@lrz.tum.de.|Klinik und Poliklinik für Neurologie, Technische Universität München, Klinikum rechts der Isar, Ismaninger Str. 22, 81675, Munich, Germany. deschauer@lrz.tum.de.
authors.forename: Marcus
authors.initials: M
authors.lastname: Deschauer
mesh_terms: D000328:Adult; D000368:Aged; D004252:DNA Mutational Analysis / Q000379:methods*; D005260:Female; D005858:Germany; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D008297:Male; D008875:Middle Aged; D049288:Muscular Dystrophies, Limb-Girdle / Q000235:genetics*; D055815:Young Adult
keywords: Gene panel; Limb-girdle muscular dystrophies; Targeted next-generation sequencing